NOPHO / NOBOSnopho.org/.../NOPHO-NOBOS-Programbok-web.pdf · 2 NOPHO / NOBOS MEETING AND CONGRESS...

Progr amme and Abstr act Book

NOPHO / NOBOS A N N U A L M E E T I N G9 – 1 3 May 2014 – Bergen – Norway


Contents

Organising committees ............................................. 2

Practical information .............................................. 9

Welcome ...................................................................... 11

Sponsors and exhibitors ......................................... 12

Map of Bergen ........................................................... 18

Social programme ..................................................... 20

NOPHO programme .................................................. 22

Invited speakers .................................................. 28

Oral presentations ............................................. 42

Poster presentations .......................................... 62

NOBOS programme ................................................... 92

Keynote speakers ................................................ 96

Oral presentations ........................................... 102

Poster presentations ......................................... 114

2 3N O P H O / N O B O S M E E T I N G A N D C O N G R E S S – B E R G E N 2 0 1 4 N O P H O / N O B O S M E E T I N G A N D C O N G R E S S – B E R G E N 2 0 1 4

Organising committees

NOPHO

Maria Winther Gunnes head of organising committee

Martha Dirdal

Dorota Wojcik

NOBOS

Sunniva Helland head of organising committee

Marianne Bentzen

Marianne Bøe

Ida Kari Ivarhus

Kjerstin Mongstad

Jorid Skjenken

Britt-Ingunn Wee Sævig

PCO

Inger Lise Ravnanger

Trine Haatuft Mjellem

Bergen Kongress & Kultur AS

kongress.no

Cover illustration: Malerduoen Bringager & Malmstrøm

Design and layout: IMP kommunikasjon / Sviggum

jernkontroll.hver dag.

www.legemiddelverket.no

NO

1203

0297

54



NO

1203

0297

54



NO

1203

0297

54

Rare?It depends how you look at itTo us, there is no difference between a disease affecting 300 million people and a disease affecting 300 people

sigma-tau.co.ukSigma-Tau Pharma Ltd. 2014-ST-006 April 2014

Dedicated to providing new therapies and new hope to people suffering from rare and neglected diseases

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KI14

659

An expertly written and practical handbook

Management of children with inherited and acquired bleeding and clotting disorders

SickKids Handbook of Pediatric Thrombosis and HemostasisEditors: Victor S. Blanchette, Toronto, Ont.Vicky R. Breakey, Hamilton, Ont.Shoshana Revel-Vilk, Jerusalem

XVIII + 254 p., 23 fig., 9 in color, 9 algorithms, 59 tab., soft cover, 2013CHF 98.– / EUR 82.– / USD 115.00ISBN 978–3–318–02197–4

Written and reviewed by international experts in the � eld, this handbook is intended for health care professionals involved in the assessment and care of children with inherited and acquired bleeding and clotting disorders, including general and specialist pediatricians (in particular intensivists, neonatologists, cardiolo-gists/cardiac surgeons, rheumatologists and nephrologists), he-matologists/oncologists (pediatric and adult), as well as medical trainees, nurses, nurse practitioners and pharmacists.

www.karger.com/sickkids

Pediatric and Adolescent Hematology

Editors: Angela E. Thomas, EdinburghChristina Halsey, Glasgow

VIII + 178 p., 13 fig., 19 tab., hard cover, 2014List price: CHF 148.– / EUR 123.– / USD 174.00Special price: CHF 104.– / EUR 86.– / USD 122.00ISBN 978–3–318–02422–7

In this book an internationally acclaimed panel of authors, each chosen for expertise in their � eld, have produced a state-of-the-art collection of review articles focusing on the very latest advances and controversies in the management of pediatric and adolescent hematological problems.Providing an up-to-date look at both speci� c hematologic dis-orders and also hematologic problems that arise in association with systemic disease, this book is essential reading not only for pediatric and adult haematologists but also for pediatricians, pediatric or hematologic specialist nurse practitioners and pedi-atric pharmacologists.

Go to www.karger.com/pamed17 and use the promotional code PedHem14 to profi t from this special off er.Prices subject to change

EUR price for Germany, USD price for USA and Latin America only

Karger – Medical and Scientific PublishersCH–4009 Basel, Switzerland

[email protected], f: +41 61 306 12 34www.karger.com

Pediatric and Adolescent Hematology

, Edinburgh, Glasgow

VIII + 178 p., 13 fig., 19 tab., hard cover, 2014List price: CHF 148.– / EUR 123.– / USD 174.00Special price: CHF 104.– / EUR 86.– / USD 122.00

Pediatric and Adolescent Medicine

Editors: D. Branski, W. Kiess

Vol. 17

Controversies in Pediatric andAdolescent HematologyEditors

A.E. ThomasC. Halsey

Hjælpdanske børn med kræft

Søg midler til forskning, uddannelse,møde- og konferencedeltagelse

Læs vejledningen påwww.boernecancerfonden.dk

Ansøgningsfrist den 1. oktober hvert år

24112_170x240_BCF_annonce.indd 1 04/04/14 14.20

Vi tilbyr verdifulle legemidler til pasienter med sjeldne sykdommerSobi fører og utvikler innovative legemidler for å hjelpe pasienter med sjeldne sykdommer og store medisinske behov.

Viktige behandlingsområder er blodsykdommer, infl ammasjonssykdommer, genetiske sykdommer og kreftterapi.

Innen disse områdene ønsker vi å øke kunnskapen om sjeldne sykdommer gjennom våre nettverk med pasienter og deres familier, helsevesenet og myndigheter, og på den måten bidra til et bedre liv for pasientene.

Sobi har fl ere samarbeidsprosjekter med OCC innen kreft og blodkreft behandling. Våre forskningsprosjekter i sen klinisk fase er primært rettet mot nye legemidler innenfor hemofi li A og B, samt forebygging av veksthemming hos for tidlig fødte barn.

Fakta om Sobi

Swedish Orphan Biovitrum, Sobi, er et ledende europeisk spesiallegemiddelfi rma der hele verdikjeden fra forskning og utvikling, produksjon, distribusjon, markedsføring og kundestøtte er representert.

Vår produktportefølje består av mer enn 40 markedsførte produkter og fl ere prosjekter i sen klinisk fase.

Vår organisasjon dekker ett 20-talls land i Europa samt våre nyetablerte datterselskaper i USA og Midt-Østen. Vi er også representert gjennom partnere i Israel, Sør-Korea, Australia og New Zealand.

Mer informasjon fi nnes på www.sobi.com

Mez

e D

esig

n P

hoto

: Dav

id B

icho

www.sobi.com

49017_Sobi_Annonse_A4.indd 1 07.08.13 15.39

Pr actical informationMeeting venueRadisson Blu Royal Hotel, BergenBryggen 5, 5003 Bergen radissonblu.com/royalhotel-bergen

The airport shuttle bus stops directly outside the conference venue. The driver will announce the stop upon request.

Registration and Conference SecretariatSaturday May 10 .......................... 16.00–19.00Sunday May 11 ............................ 07.30–10.00

Name badgeYour name badge gives you admission to the scientific sessions, lunch and coffee breaks. Your badge must be worn at all times at the conference venue.Lost/misplaced badges can be replaced at theRegistration desk at a cost of NOK 50.

Official languageThe official working language of the meeting is English.

Coffee breaksCoffee is served in the exhibition area.

LunchA two course lunch will be served Sunday and Monday, and a light lunch will be served before departure on Tuesday.

Internet accessThere is free wi-fi at the congress venue. Log on information is:Network name: Meeting DelegatePassword: JvzU | VspJ ( four letters in two separate boxes )

Smoking policyThe congress venue is entirely non smoking.

Presentations ( invited speakers )Presentations should be handed to the technician at the latest 2 hours before your session starts.

Tourist information in BergenThe Tourist information at Vågsalmenningen 1 (near the Fish Market) is open daily 08.30–22.00.

Trip up Mount FløienWhile in Bergen we recommend taking the funicular up Mount Fløien, and would therefore like to offer you tickets for free. These tickets will be available at the registration desk from Sunday after 12.00.

ShoppingThe shops at Bergen Storsenter and Galleriet are open Mon–Fri 09.00–21.00 and Sat 09.00–18.00.

Transport to Bergen Airport Flesland

Taxi: The taxi fare to Bergen Airport Flesland (20 km) is about NOK 450.The airport bus: (Flybussen) departs every 15 min from Radisson Blu Royal Hotel and costs NOK 90 for a one way ticket.


9N O P H O / N O B O S M E E T I N G A N D C O N G R E S S – B E R G E N 2 0 1 4

http://www.radissonblu.com/royalhotel-bergen

Welcome

Dear NOPHO/NOBOS friends, colleagues, sponsors and invited guests and speakers

On behalf of the organising committee and the Pediatric Oncology Department at Haukeland University Hospital we would like to welcome you all to the 32nd Annual NOPHO meeting and the 10th Biannual NOBOS meeting! We are honored to host this event here in beautiful Bergen, Norway’s second largest city.

Bergen was founded by King Olav Kyrre in 1070, and was part of the Hanseatic League from the 14th century until around 1750, and one of four Hanseatic League centres were found in Bergen. Today, Bergens old quayside, Bryggen, is part the UNESCO list of World Heritage Sites, and we are proud to host the confer-ence in the SAS Radisson Hotel situated at Bryggen.

The Pediatric Oncology Department at Haukeland University Hospital is Norway’s second largest pediatric oncology department, and is responsible for pediatric

cancer and hematology patients from the wide geo-graphical area of western Norway, covering the counties of Hordaland, Rogaland and Sogn og Fjordane.

We are pleased to present a varied and interesting sci-entific program, with well recognized invited speakers in their respective fields, from across the globe.

We would like to thank all of our sponsors and contribu-tors, especially our Gold Sponsors; this meeting would not have been possible without the generous support by all of our collaborating partners.

We hope you will all have a wonderful scientific con-ference as well as fruitful social gatherings where you will continue to develop relations with your fellow members of the NOPHO/NOBOS family!

On behalf of the Organising Committee

Maria Winther GunnesNOPHO

Sunniva HellandNOBOS

Photo: Bergen Tourist Board/Robin Strand - visitBergen.com


Sponsor s and exhibitor s

GALENAdvancing Human Health

Gold Sponsors

Bronze Sponsors

Exhibitors

Other Sponsors

GlaxoSmithKline

Light Integra Technology

Medac

MSD Norge

Pierre Fabre Pharma Norden

Therakos

Grimsgaards stiftelse

Hordaland fylkeskommune

Mary Béves stiftelse

Gilead

Helse vest

Strømberggruppen as

Vi tilbyr verdifulle legemidler til pasienter med sjeldne sykdommerSobi fører og utvikler innovative legemidler for å hjelpe pasienter med sjeldne sykdommer og store medisinske behov.

Viktige behandlingsområder er blodsykdommer, infl ammasjonssykdommer, genetiske sykdommer og kreftterapi.

Innen disse områdene ønsker vi å øke kunnskapen om sjeldne sykdommer gjennom våre nettverk med pasienter og deres familier, helsevesenet og myndigheter, og på den måten bidra til et bedre liv for pasientene.

Sobi har fl ere samarbeidsprosjekter med OCC innen kreft og blodkreft behandling. Våre forskningsprosjekter i sen klinisk fase er primært rettet mot nye legemidler innenfor hemofi li A og B, samt forebygging av veksthemming hos for tidlig fødte barn.

Fakta om Sobi

Swedish Orphan Biovitrum, Sobi, er et ledende europeisk spesiallegemiddelfi rma der hele verdikjeden fra forskning og utvikling, produksjon, distribusjon, markedsføring og kundestøtte er representert.

Vår produktportefølje består av mer enn 40 markedsførte produkter og fl ere prosjekter i sen klinisk fase.

Vår organisasjon dekker ett 20-talls land i Europa samt våre nyetablerte datterselskaper i USA og Midt-Østen. Vi er også representert gjennom partnere i Israel, Sør-Korea, Australia og New Zealand.

Mer informasjon fi nnes på www.sobi.com

Mez

e D

esig

n P

hoto

: Dav

id B

icho

www.sobi.com

49017_Sobi_Annonse_A4.indd 1 07.08.13 15.39

Hjælpdanske børn med kræft

Søg midler til forskning, uddannelse,møde- og konferencedeltagelse

Læs vejledningen påwww.boernecancerfonden.dk

Ansøgningsfrist den 1. oktober hvert år

24112_170x240_BCF_annonce.indd 1 04/04/14 14.20

KIWANIS CLUB SOTRA


Welcome to Bergen – Gateway to the Fjords

Bergen is located on the south-western coast of Norway, with its centre situated between a group of mountains known collectively as De syv fjell ( ”The seven mountains” ).

Bergen is host to part of the country’s large oil industry, as well as deep sea operations. Its harbours are used by everything from small pleasure vessels to cruise ships and cargo vessels, and are the base of many of the country's fishing vessels.

Bergen has been a focal point of cultural and commercial activity from medieval to modern times. Its population of 272 000 proudly invites you to share the bustling

maritime atmosphere, the rich architectural heritage and the cultural and academic institutions of their home city. Located in the heart of the famous fjords, Bergen is also known as the Gateway to the Fjords.

We are certain that the City of Bergen would give the participants a long lasting memory as and extended value; this includes the scenery, the old Hanseatic quay and housing structure.

Photo: Bergen Tourist Board / Willy Haraldsen - visitBergen.com

Fløibanen Photo: Pål Hoff - visitBergen.com Zachariasbryggen Photo: Bergen Tourist Board / Robin Strand


Restaurants:• Matbørsen, SmåStrandgaten; close to Radisson

Bryggen and the fish market, an Old Stock market with unique fresco paintings from 1918–1923, now “Food Market” with several restaurants

• Bølgen & Moi, VågSalmenningen 16; close to Radisson Bryggen and the fish market

• Lysverket, raSmuS meyerS allè 9. Close to the museums and “lille Lungårdsvann”. A quite new restaurant and probably the best in town at the moment. Pricy.

• Nama Japanese Fusion, lodin leppS gt 2B. Close to Bryggen, best sushi restaurant in town

• Enhjørningen, Bryggen. One of the best seafood restaurants in Bergen

• Bryggeloftet, Bryggen. Traditional Bergen restaurant, located at Bryggen

• Potetkjelleren, Kong oScarS gt. 1B. Traditionally one of the best restaurants in town. Pricy.

• Restaurant 1877, KjøttBaSaren, VetrlidSalmenning 2. Close to Bryggen and the fish marked

• Maharaja, roSenKranzgt 5. Close to Bryggen. Good Indian food.

• Red Sun, Kong oScarS gt 4. Close to Bryggen. Asian Fusion.

• Escalon, VetrlidSalmenningen 21. Close to Bryggen. Very good Tapas food.

Bars: • Don Pippo, chriStieS gt 11;

small, cosy wine bar in city centre• Altona, c. SundtS gt 22;

old cellar, now wine bar, with lots of atmosphere• Henrik, engen 10. Close to the theatre, laid-back

atmosphere, the bar in town with the largest number on microbrewery beers on tap

• Pingvinen, VaSKerelVen 14. Cool retro bar in the city centre

Cafès:• Kaffemisjonen, øVre KorSKirKealmenning 5;

probably the best coffee in town• Smaksverket, Rasmus Meyers allè 3; close to the

main museums and “lille Lungårdsvann”

Shopping: • Galleriet, torgalmenningen; large shopping centre

in town, by the large square “Torgalmenningen”• Kløverhuset, Strandgaten 13–15. • Illums Bolighus• Skomakerstredet, small, cosy pedestrian street with

speciality shops and second-hand shops• Bergen Storsenter, large shopping mall by the

railway station

Attractions: • Fløybanen Funicular (tickets free of charge available

from the registration desk), close to Bryggen • Akvariet, Bergen Aquarium, Nordnesbakken 4

Museums: • KODE• Rasmus Meyer

Tips from the locals

Photo: Bergen Tourist Board / Per Nybø Photo: Bergen Tourist Board / Jan M. Lillebø


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1 Radisson SAS Hotel Bryggen 2 Grieghallen 3 USF Verftet 4 The Blue Stone 5 Kreftforeningen

Social progr amme

Saturday May 10

Guided tour of the composer Edvard Griegs home, including concert. Aproximate duration 2 hrs. Small extra cost ( 100 NOK ) for participation, NB! Limited spaces available!Bus departs at 2 pm from radisson Blu royal

Meet-and-greet and poster sessionCome and enjoy a bit of socialising with colleagues and friends before exploring the city on your own for the rest of the evening! 7–9 pm at radisson Blu royal Hotell

Sunday May 11

NOBOS DinnerUSF is located on the pier accommodating Bergen's largest outdoor restaurant in the summertime, where 500 guests can enjoy the most beautiful fjord views.usf Verftet at 6 pm

NOPHO dinner Cornelius has an idyllic location, right on the waterfront just outside Bergen. Here, both fishingboats and divers deliver their best catch of the day. Boat departs at 7 pm

Monday May 12

NOBOS / NOPHO Fun and RunRise and shine early to join the fun. Meeting place will be outside Radisson Blu Royal Hotell Bryggen. Shades are optional.radisson Blu royal Hotell at 6.30 am

The annual NOBOS / NOPHO dinner The annual dinner will be held at Grieghallen in the city centre. Dinner, entertainment and dancing until the late hours! GrieGHallen at 7.30 pm

USF Verftet Cornelius Photo: Truls J. Løtvedt

Grieghallen Photo: Bergen Tourist Board / Willy Haraldsen Bryggen Photo: Bergen Tourist Board / Robin Strand Troldhaugen Photo: Bergen Tourist Board / Per Nybø


Fr iday 9 May

08:30–12:00 NOPHO Working groups (see separate program)

13:00–17:00 NOPHO Working groups

Sat u r day 10 May



13:00–15:00 Young NOPHO educational session Chair: Marta Dirdal

Statistics in clinical trials, challenges and pitfallsEva Skovlund, Oslo

Evening Poster session / “Meet-and-greet” 19–21

Sunday 11 May

08:30–09:00 Opening ceremony and info from the organizers

09:00–10:30: Joint session NOPHO/NOBOSChair: Britt Ingunn Sævig

How does cancer treatments affect the developing child?Marianne Straume, Bergen

10:30–11:00: Coffee break

11:00–11:45: Ethical dilemmas when treating seriously ill childrenTrond Markestad, Bergen

11:45–12:30 Ethics Chair: Trond MarkestadFree papersO1 A Nordic platform for clinical ethics in pediatric oncologyPernille Wendtland Edslev, AarhusO2 Treatment decisions in pediatric health care- Who’s the one to decide? Lisa Törnudd, LinköpingO15 Conceptual clarity of values in end-of-life deliberations in pediatric oncologyAnders Castor, Lund

12:30–13:45 Lunch

13:00–17:00 InfectionsChair: Maria Winther Gunnes

13:45–14:30: Fever and neutropenia in pediatric cancer patients; is a choice between outpatient v/s inpatient management a routine one? Critical review and recommendations.Lillian Sung, Toronto

14:35–15:10 Implementing a diagnostic strategy for management of invasive fungal disease in hemato-oncologySamir Agrawal, London

15:10–15:30 Coffee break

15:30–16:15 Challenges in the diagnosis and management of invasive fungal infections in 2014Paul Verweij, Nijmegen

15:45–16:00 Discussion with speakers

16:15–16:45 Late-effects Chair: Ellen Ruud

Free papersO3 Hospital admissions for respiratory disorders in adult life after childhood cancer in Scandinavia (ALiCCS) – A population-based cohort studyThorgerdur Gudmundsdottir, Danish Cancer Society Research Center

O4 Diseases of renal function and bone metabolism following treatment of early-onset cancer. A registry-based studyMarika Grönroos, Turku

Info from organizers

Evening NOPHO dinner Cornelius, boat departs at 19:00

NOPHO progr amme


Mo nday 12 May

06:30–08:00 Fun and Run

08:30–10:15 Free papersLeukemia Chair: Bem ZellerO5 Hepatic Veno-Occlusive Disease in Children with Acute Lymphoblastic Leukemia During Maintenance Therapy with Continuous AsparaginaseSilvia De Pietri, Rigshospitalet, CopenhagenO7 Intra-tumoral heterogeneity of T-ALL leukemic blasts at diagnosis and follow-up; implications for minimal residual disease detectionNina Friesgaard Øbro, Rigshospitalet, CopenhagenO8 Genomic characterization of dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemia Vasilios Zachariadis, Karolinska, StockholmMiscellaneous

O9 RESPECT – A feasibility study of a school re-entry, physical- and social activity intervention for school children with cancerAnne Sofie Helms, Rigshospitalet, CopenhagenO10 Flow cytometric measurement of platelet associated immunoglobulin in children with newly diagnosed immune thrombocytopeniaOle Haubjerg Nielsen, AalborgO11 PPM1D/Wip is a novel neuroblastoma oncogene and potential therapeutic target in high-risk neuroblastomaJelena Milosevic, Karolinska, StockholmO12 Pediatric germ cell tumors in Denmark, 1985–2012Madeline Evers, Rigshospitalet, Copenhagen

10:15–10:45 Coffee break10:45–11:45 NOPHO Lecture:

Chair: Secretary General NOPHO, Marit HellebostadMedulloblastoma todayBirgitta Lannering, Gothenburg

11:45–13:00 Lunch13:00–17:00 Bone marrow failure / Myelodysplastic syndrome /

Stem cell transplantation – Mary Béve SymposiumChair: Dorota Wojcik

13:00–13:45 Clinical approach to inherited bone marrow failure syndromesInderjeet Dokal, London

13:50–14:35 Novel cellular treatment approaches after allo-SCTPeter Bader, Frankfurt

14:35–15:00 Coffee break15:00–15:45 Diagnosis and management of childhood MDS and JMML

Henrik Hasle, Århus15:45–16:00 Panel discussion and info from organizers

16:00–18:00 NOPHO General Assembly

19:30 Annual dinner, Grieghallen

tu e S day 13 May

08:30–09:15 SarcomasChair: Finn Wesenberg

Recent developments in osteosarcomaStefan Bielack, Stuttgart

09:15–10:00 Free papers O13 Late mortality among Finnish 5-year survivors of early onset cancerPäivi Lähtenmäki, Turku

O14 The SALUB registry: survivorship passport and nationwide registration of late-effects after childhood cancer in SwedenCecilia Petersen, Karolinska, Stockholm

O16 Incidence of thrombosis in children treated according to non-HR NOPHO ALL 2008- a prospective single center studyEllen Ruud, Rikshospitalet, Oslo

10:00–10:45 The SSG central register. 6000 patients after 25 years of monitoring referral and treat-ment in orthopedic soft tissue sarcomaClement Trovik, Bergen


11:15–12:00 Free papers O17 Hyperferritinemia in severely ill patients: associations with clinical and laboratory findingsTatiana Greenwood, Karolinska, Stockholm

O18 Thalassemia and Diamond Blackfan Anemia in Sweden. Data from the Nordic Transfusion RegistryUlf Tedgård, Skåne University Hospital

O19 Iron deficiency and iron deficiency anemia in toddlers in Oslo. Is there a differ-ence between children of different ethnic backgrounds?Einar Stensvold, Rikshospitalet, Oslo

12:00 Presentation of next years meeting

12:10 Closing remarks from the organizers

12:15 Lunch bag / small buffet and departure


Fr iday 9 May

Activity Room #09:00–12:00 NHL Dræggen 1 10

12:00–18:00 Young Nopho Dræggen 3 30

12:00–18:00 LLC Dræggen 4b 30

16:00–18:00 ALL 2008 Dræggen 4a 20

18:00–19:00 ALL relapse Dræggen 4a 10

Sat u r day 10 May

Activity Room #07:30–08:50 Novel Therapy Working Group Dræggen 4a 10

07:30–09:00 ALL 2016 Dræggen 3 10

08:00–10:00 Late effect Dræggen 4b 15

09:00–13:00 Brain Tumors Dræggen 4a 14

09:00–12:00 LLC Dræggen 3 30

13:00–18:00 Nopho board Dræggen 4b 20

13:00–15:00 Red cell disorder Dræggen 4a 10

20:00–22:00 Histiocytose Dræggen 4b 20

Sunday 11 May

Activity Room #07:30–14:00 Thrombosis and hemostasis Dræggen 4a 8

NOPHO Working groups Progr amme

Photo: Bergen Tourist Board / Per Eide

26 N O P H O / N O B O S M E E T I N G A N D C O N G R E S S – B E R G E N 2 0 1 4

INVITED SPEAKERS

Inderjeet DokalProfessor, Centre for Paediatrics, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London Barts Health NHS Trust, London

Inherited bone marrow failure syndromes

The inherited bone marrow (BM) failure syndromes are a diverse group of disorders characterized by BM failure usually in association with one or more extra-haematopoietic abnormality. The BM failure, which can involve all or a single lineage, often presents in childhood but this may not be until adulthood in some cases. Furthermore, some patients initially labeled as “idiopathic aplastic anaemia” are cryptic presenta-tions of these genetic syndromes. Significant advances in the genetics of these syndromes have been made with more than fifty disease genes identified to date. These advances have provided a better understanding of normal haematopoiesis and how this is disrupted in patients with BM failure. Additionally, as these disorders are usually associated with developmental

abnormalities and an increased risk of cancer they are providing insights into human development and the genesis of cancer. In the clinic, genetic tests stemming from the recent advances are facilitating diagnosis and personalized management. Haematopoietic stem cell transplantation using fludarabine based protocols has improved outcomes significantly; management of some of the non-haematopoietic complications remains a challenge.

Inderjeet Dokal graduated in Medicine from the University of Leicester in 1983. He moved to Hammersmith Hospital (London) in 1984 where he received his post graduate clinical and research training. He was appointed Con-sultant in Paediatric Haematology in 1995 and was conferred the title of Professor of Haematology at Imperial College in 2003. In

2006 he was recruited to the Chair of Child Health at Barts and The London/Queen Mary University of London.His principal research interest is the patho-physiology of aplastic anaemia (AA)/bone marrow failure. Over the past 20 years his group has determined the genetic basis and pathophysiology of several sub types of bone

marrow failure. This has shown the impor-tance of telomerase and telomeres in humans and the consequences of their dysfunction. Current research is focussed on elucidating the genetic basis and pathophysiology of the many uncharacterized cases of dyskeratosis congenita, aplastic anaemia, myelodysplasia and related disorders.

Inderjeet Dokal Clinical Approach to Inherited Bone Marrow Failure Syndromes

Peter BaderNovel cellular treatment approaches after allogeneic stem cell transplantation: from specific immunotherapy to tolerance induction

Henrik HasleDiagnosis and management of childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia

Lillian SungFever and neutropenia in pediatric cancer patients: is a choice between outpatient v/s inpatient management a routine one? Critical review and recommendations

Stefan BielackRecent developments in osteosarcoma

Clement Trovik The Scandinavian Sarcoma Group Central Register. 6000 patients after 25 years of monitoring referral and treatment in Orthopaedic Soft Tissue Sarcoma

Samir AgrawalImplementing a Diagnostic Strategy for Management of Invasive Fungal Disease in Haemato-Oncology

Paul VerweijChallenges in the diagnosis and management of invasive fungal infections in 2014

Marianne StraumeHow does cancer treatment affect the developing child, and what can we do to help children integrate the hardship they experience

Trond MarkestadEthical dilemmas when treating seriously ill children

Eva SkovlundStatistics in clinical trials – challenges and pitfalls

Overview


Henrik HasleProfessor, Department of Pediatrics Aarhus University Hospital Skejby, Denmark

Diagnosis and management of childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia

Myelodysplastic and myeloproliferative disorders are rare in children. Contemporary classification includes three main groups; myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML), and the myeloid leukemias of Down syndrome (ML-DS). MDS is subdivided into refractory cytopenia of child-hood (RCC) and advanced MDS (RAEB). Some patients have underlying constitutional bone marrow failures. Hypoplastic RCC has a very favorable outcome with immunosuppressive therapy and hematopoietic stem cell transplantation (HSCT) as salvage option. The only curative therapy for advanced MDS is HSCT. The conditioning regiment and GvHD prophylaxis

have major impact on the outcome. Genetic aberration in the RAS signal transduction pathway is found in most patients with JMML and has contributed major insight in the pathogenesis of JMML and facilitates the diagnosis. JMML with CBL mutation represent a special group that may regress spontaneously like in infants with JMML and Noonan syndrome. Azacitidine is being tested as a possible bridge to HSCT for advanced MDS and JMML Reduced AML therapy is very suc-cessful in ML-DS.

[email protected]

Henrik Hasle is professor in pediatric hematol-ogy/oncology at the department of Pediatrics, Aarhus University Hospital Skejby in Aarhus Denmark.Henrik Hasle trained in epidemiology, hema-tology and pediatrics at Odense University Hospital, where he also completed a research fellowship in pediatric oncology with a thesis on myelodysplastic syndrome. Since 2000

consultant and associate professor in pediatric hematology/oncology at Aarhus University Hospital Skejby in Aarhus and was awarded full professor in 2009.Henrik Hasle is a founding member of the European Working group on Myelodysplastic Syndromes in Childhood (EWOG-MDS) and served as chairman of the group 1998-2002. Henrik Hasle was the chairman of the AML

group of the Nordic Society for Pediatric He-matology and Oncology (NOPHO) 2002 to 2010.Henrik Hasle is the author or coauthor of more than 170 peer reviewed journal articles mainly dealing with myeloid leukemia in chil-dren and genetic predisposition to cancer.

Peter BaderProfessor, Goethe University and University Childrens Hospital, Frankfurt, Germany

Novel cellular treatment approaches after allogeneic stem cell transplantation: from specific immunotherapy to tolerance induction

Immunotherapy has progressively acquired an impor-tant part in the treatment of children with refractory/resistant hemato-oncological diseases. Its ultimate goal is that of increasing the immunological driven anti cancer effect without causing further immunological complica-tions. Through recent experience some basic principles in the use of immunotherapy have become clear: it has better success rate when applied in the pre-emptive setting and it should be preceded by lymphodepletion. It is therefore straightforward to think that the stem cell transplantation setting could be a perfect match

for this kind of therapy. The presentation summarizes some of the many different strategies that are nowadays under pre-clinical and clinical evaluation, mostly in the pediatric field, and hints at their possible application in the allogeneic stem cell transplantation field.

After graduating at the University Tübingen, Prof. Bader started his education to become a pediatrician at the University Children’s Hospital in Tübingen under the supervision of Prof. Dr. Dietrich Niethammer. In 2000, he was a pointed as attending physi-cian in the Children’s Hospital and continued with his research program (see below). After successful publication of several manuscripts as first author he received the “Habilitation” and received a lecturer title. He was awarded a Full Professorship at the Goethe University in Frankfurt at the University Children’s Hospital and appointed as the Head of the Division for Stem Cell Transplantation and Immunology in 2004. Since then he is responsible for the Stem Cell Transplantation Program and he

become Vice Director of the Department for Children and Adolescents in 2010.

Research Interest and Program:He has started his research in the field of pediatric stem cell transplantation. The pre-vention of relapse post transplant has become one of the major challenges. Prof. Bader’s Group has developed PCR based techniques for the quantitative analysis of chimerism and minimal residual disease (MRD). Based on several large grants the Group has performed prospective trials were it could be shown that using molecular techniques relapses could be anticipated in a great cohort of children’s after allogeneic stem cell transplantations.Since his move to Frankfurt in 2004 he built up

a large transplant program focusing on T-cell depleted transplants using different donors, especially HLA non-identical relatives after re-duced intensity conditioning. Based on these activities he successfully widened the research profile of his group towards cellular therapies post transplant. This includes tumor specific T-cell transfer and cytokine induced killer cell (CIK) including chimeric antigen receptor (CAR) modified therapies for the treatment of children with malignancies. These projects have been recently awarded with two large research grants. An additional focus of this group is on the generation and clinical use of mesenchymal stromal cells.


Stefan BielackProfessor and Head of Department of Pediatric Oncology and Hematology, Olgahospital, Stuttgart, Germany. Cooperative Osteosarcoma Stucy Group COSS

Recent developments in osteosarcoma

The past decades have witnessed little improvement in survival from osteosarcoma. Nevertheless, there have been many important developments: Modern tech-niques, particularly MRI, offer very precise imaging of the tumor, a prerequisite for the ever increasing use of limb-salvage surgery. Expandable endoprostheses allow limb-salvage even in growing children. European and American groups collaborate in the EURAMOS1-trial to better define standard medical therapy. Results of the Good Responder randomization (standard chemo-therapy +/- pegylated interferon alpha) were presented at ASCO 2013, those of the Poor Responders are

expected for 2015. Drugs currently under discussion include mifamurtide, sorafenib, and various other tar-geted therapies. Novel radiotherapy techniques, such as carbon ion radiation, may offer hope for patients with unresectable primaries. At recurrence, surgery remains the mainstay of treatment, while the debate about the role of (adjuvant) second line treatments continues. Work-Package 7 (bone sarcoma) of the ENCCA-FFP7 network currently works to integrate clinical trials and tumor biology research.

Prof. Stefan Bielack is a pediatric oncologist and head of the Department of Pediatric Oncology, Hematology, Immunology; Gas-troenterology, Rheumatology and General Pediatrics at Klinikum Stuttgart - Olgahos-pital, Stuttgart, Germany. His main scientific and clinical interest lies in the field of bone sarcoma, particularly osteosarcoma. Ste-fan Bielack is chairman of the Cooperative

German-Austrian-Swiss Osteosarcoma Study Group COSS, ECT project leader of the Eu-ropean and American Osteosarcoma Study EURAMOS1, and leader of the bone tumor work package of the European Network for Cancer Research in Children and Adolescents ENCCA. He has served as President of the European Musculo-Skeletal Oncology Society EMSOS and board member of the German

Society for Pediatric Oncology and Hematol-ogy GPOH and is currently a member of the board of the Southern German Society for Pediatric and Adolescent Medicine SGKJ. He is a current member of the editorial boards of Cancer Treatment Reviews and the Journal of Adolescent and Young Adult Oncology.

Lillian SungAssociate Professor and Scientist, The Division of Haematology / Oncology, Hospital for Sick Children, Toronto, Canada

Fever and neutropenia in pediatric cancer patients: is a choice between outpatient v/s inpatient management a routine one? Critical review and recommendations

Fever and neutropenia (FN) is a common complica-tion of cancer therapy. Traditional approaches have included admission to hospital with administration of intravenous antibiotics. This presentation will review the evidence supporting outpatient management with oral or intravenous antibiotics and discuss parental preferences and considerations.

Dr. Lillian Sung is an Associate Professor and Scientist at The Hospital for Sick Children, Toronto, Ontario, Canada. She is certified by the Royal College of Physicians and Surgeons of Canada in the specialties of pediatrics, in-fectious diseases, hematology and clinical investigation. During her training, she also completed a PhD in Clinical Epidemiology from the Department of Health Policy, Man-agement and Evaluation at the University of Toronto in 2004. Since her faculty appoint-ment, she has developed a clinical research

program focused on supportive care for children with cancer and more specifically, understanding predictors of infectious com-plications in pediatric leukemia and develop-ment of a new measure of oral mucositis in pediatric cancer. Her methodological focus is on randomized and observational trials, meta-analysis, and patient-reported outcomes. She is supported by a New Investigator award from the Canadian Institutes of Health Research. She was awarded an Early Research Award by the Ontario Ministry of Health and Innova-

tion and she is the principal investigator on multiple operating grants from the National Cancer Institute of Canada and the Canadian Institutes of Health Research. She currently is also the principal investigator of an R21. She was the recipient of the Excellence in Cancer Research - William E. Rawls Award in Cancer Control in 2009, awarded from the Canadian Cancer Society. Dr. Sung is also the Chair of Cancer Control in the Children’s Oncology Group (COG), which oversees all studies of supportive care.


Clement S. TrovikProfessor dr.med Departments of Musculoskeletal Tumour Service, Haukeland University Hospital, Bergen

The Scandinavian Sarcoma Group Central Register. 6000 patients after 25 years of monitoring referral and treatment in Orthopaedic Soft Tissue Sarcoma

Based on the mean population of Norway, Finland, Iceland and Sweden 1987-2011 (18.6 mil) and an annual incidence of STS in extremities and trunk wall of 2-3/100.000, there should have been approximately 11.000 (9000-13.000) sarcomas registered in a 25 year period. 6127 are in fact in the register. 5858 have complete registration of key variables.11 institutions have been reporting to the register. From Norway and Sweden, five institutions, representing approximately 70% of the population, have been reporting all their cases consistently during the entire period. From Finland, two institutions representing approximately 50% of the population, have been reporting most years. Iceland has just started reporting.The five consistently reporting institutions are treating approximately 90% of the cases in their region. The

remaining institutions have mostly reported all their treated patients during certain time periods, and not at all during other periods. The register may therefore be considered representative for the population of Scandinavia, treated at the reporting institutions.59% of patients are referred to a sarcoma centre untouched, before any attempt at biopsy. There was an improvement from 51% during the first 5 years to 68% during the last.50% had wide or better margins at surgery. There seems to be a change of attitude among Scandinavian surgeons concerning the importance of a wide margin, parallel to an increase in use of radiotherapy. Wide margins are now achieved significantly less often than 20 years ago.For the consistently reporting institutions, the rate of follow-up is 97%.

Clement S. Trovik, Professor dr.med is a spe-cialist in general surgery and orthopedics and leader of the Bergen Sarcoma Centre, one of two sarcoma centers in Norway. He achieved his PhD in 2000 and became Norways first professor in orthopedic oncology in 2012.

Professor Trovik has for many years been the leader of the surgical group and of the central registry in the Scandinavian Sarcoma Group (SSG). Associate Editor in Sarcoma and ref-eree for several journals. He has around 30 publications.

Samir AgrawalBSc (Hons), MB ChB, FRCP, FRCPath, PhD

Senior Lecturer in Haematology, Queen Mary University of London and Consultant Haemato-Oncologist at St Bartholomew’s Hospital and The Barts Health NHS Trust

Implementing a Diagnostic Strategy for Management of Invasive Fungal Disease in Haemato-Oncology

The development of care pathways for IFD manage-ment involves not just the clinical team looking after the patient, but everyone required in the pathway must be involved in order to have “ownership” of the pathway: radiology, microbiology, infectious disease and respiratory physicians…This care pathway will be different in each institution and dependent on local factors. By ensuring each step of the pathway is clear, each individual knows their responsibility in the process (from the nurse on the ward to the radiologist), the chances of a successful outcome for the patient will be maximized. My presentation will focus on the current debate on management strategies for invasive fungal disease (FD) in Haemato-Oncology. I will discuss empirical

therapy versus a pre-emptive or a diagnostic-driven approach.I will describe the changes in our management algo-rithms over the last 12 years at St Bartholomew’s Hospital, London, and discuss the various factors that impact at a local level in terms of which strategy to use. This process has brought us nearer and nearer to what can be called a care pathway. A diagnostic-driven approach requires, of course, that tests (blood tests as well as imaging) are rapidly available and I will describe our experience with routine galactomannan testing and CT scanning and their limitations. Finally, future diagnostics – the lateral flow device, proximity ligation assay – will be presented.

Dr Agrawal qualified initially at the University of Bristol subsequently trained at The Royal Marsden Cancer Hospital and being awarded his PhD (in Immunology) at the University of Paris. He is a fluent French speaker. He is Director of The Stem Cell Laboratory and Head of Diagnostic Immunophenotyp-ing. He was a winner of the NHS Innovator Awards in 2006 for the introduction of new diagnostic tests for the diagnosis of human leukaemias.He has designed, funded, and implemented studies on myelodysplastic syndromes, inva-sive aspergillosis, and chronic lymphocytic

leukemia. He is a member of the UK CLL trials committee and trustee for CLLSA (the patient-led support organisation for patients in the UK with CLL), as well as a NICE review-er and the Haemato-Oncology representative on the UK IVIg initiative. His current activities in the field of invasive fungal disease are:- an ongoing diagnostic study of high-risk haematology patients looking at early di-agnosis with a novel Aspergillus PCR and investigating exhaled breath condensate for IFD diagnosis- developing clinical guidelines and integrated

care pathways for managing IFD in the high-risk haemato-oncology setting- promoting best practice and highlighting new developments through educational meetings and a new website for all interested in fungal disease (www.fungalcentral.com, currently in development) Dr Agrawal has published over 50 papers in journals such as the Journal of Clinical Investigation, Journal of Immunology, Blood, the British Medical Journal, and the Journal of Clinical Oncology.


http://www.fungalcentral.com

Paul E. VerweijMD, PhD, professor of medical microbiology and consultant microbiologist, Department of Medical Microbiology, Radboud University Medical Center, The Netherlands

Challenges in the diagnosis and management of invasive fungal infections in 2014

The timely diagnosis of invasive fungal infection (IFI) is important to allow early antifungal therapy and improve outcome. The use of biomarkers and imaging have clearly improved our ability to diagnose certain IFIs, but there are several developments that complicate early diagnosis. The taxonomy of many fungi has changed, and new species are increasingly recognized as cause of IFI. These new sibling species often differ in susceptibility to the conventional species and presents problems in treatment choice. In addi-

tion to intrinsic resistance, also in some fungi acquired resistance is increasingly found. In Candida glabrata resistance rates for fluconazole and echinocandins are increasing in some hospitals. In Europe azole resistance is an emerging problem Aspergillus fumigatus, primarily due to environmental use of azole fungicides. These developments increasingly challenge are diagnostic approach and requires new tests and approaches to patient management to be developed.

Paul Verweij is professor of medical microbiol-ogy and consultant microbiologist at the De-partment of Medical Microbiology at Radboud University Medical Center in The Netherlands. Dr Verweij received his medical degree from University of Leiden in The Netherlands. He served as registrar in medical microbiology at University Hospital Nijmegen, where he completed his PhD thesis (“Microbiological diagnosis of invasive aspergillosis”). Dr Ver-

weij then received research training at Victoria University Manchester in England. Dr Verweij’s research interests include diagnosis of invasive aspergillosis, resist-ance in moulds, and clinical studies of new antifungal agents. He has authored or coau-thored numerous articles for journals such as Antimicrobial Agents and Chemotherapy, PLoS Medicine, and the New England Journal of Medicine.

Dr Verweij is a member of several professional organizations, including the International So-ciety for Human and Animal Mycology, the European Society for Clinical Microbiology and Infectious Diseases. He is member of the executive committee of the EORTC-IDG and chairman of the Dutch Society for Medi-cal Mycology.

Eva SkovlundMSc pharm, PhD statistics

Statistics in clinical trials – challenges and pitfalls

Basic facts on elementary statistical analyses in clinical trials are presented, and common misunderstandings are discussed. The weaknesses of p-values and misun-derstandings in how to interpret them are illustrated with practical examples. The effect of sample size is presented and the difference between statistical significance and clinical relevance is highlighted, and recommendations on use of confidence intervals for effect estimates are made.

Eva Skovlund, MSc pharm, PhD statistics 1990. Since 2011 she holds her main position at the Norwegian Institute of Public Health, presently as acting director of the Division of Epidemiology. In addition holds a position as professor II at the School of Pharmacy, University of Oslo. From 2001 to 2011 she was scientific director at the Norwegian Medicines

Agency. Her main role was then to be the Nor-wegian member of CHMP at the European Medicines Agency, the body that assesses safety and efficacy of new active substances as well as all medicinal products on the mar-ket in EU/EEA. Previous experience includes: statistician Glaxo Norway, associate professor Department of Mathematics, University of

Oslo, supervisor in clinical cancer research at the Norwegian Radium Hospital (Norwegian Cancer Society), and 12 years as professor II at the Section of Medical Statistics, University of Oslo. Long experience in teaching medical statistics and supervising clinical research projects on all levels.


Marianne StraumeCand. Psychol. Psychologist Specialists in clinical psychology, speaker, crisis management

How does cancer treatment affect the developing child, and what can we do to help children integrate the hardship they experience

Children are malleable and very adaptable. This also makes them vulnerable. Children develop in relation to their genetic potential and the experiences they make. Cancer treatment in children is a very specific experience in critical and sensitive periods of their development. Cancer and cancer treatment represents great stress

for children. Children have lower integration capacity than adults. This makes children totally dependent on adults to integrate the strains they are exposed to into their psychobiographic memory. In this presentation I will discuss how adults can help children integrate the hardship they experience.

Trond Markestadprofessor of Pediatrics, University of Bergen, research coordinator at the Department of Pediatrics, Haukeland University Hospital, Bergen, research advisor at Hospital Innlandet Trust, Eastern Norway

Ethical dilemmas when treating seriously ill children

With the advances in medicine and rising and often unrealistic expectations of what medical care can provide, pressure to continue or offer futile treatment and to continue life prolonging treatment beyond what may be considered in the child’s best interest may be challenging for health care providers. Based on such experiences, The Norwegian Medical Association took the initiative to make a national guideline on how to handle such dilemmas. The guideline was published

by the Directorate of Health in 2009 and revised in 2013. The subject will be discussed with reference to this guideline.

Trond Markestad has worked within different fields of pediatrics since 1975, but mostly as a neonatologist. He is currently professor of Pediatrics at the University of Bergen, research coordinator at the Department of Pediatrics, Haukeland University Hospital, Bergen, and

research advisor at Hospital Innlandet Trust, Eastern Norway. The last 16 years he has been member, the last 8 years the chairman, of the Ethics Committee at The Norwegian Medical Association.

NOPHO/NOBOS joint session


Birgitta LanneringProfessor, University of Gothenburg, Sweden. MD, Pediatric Oncology Department, Drottning Silvias Hospital, Gothenburg

Medulloblastoma today

Which are the new insights into medulloblastoma biology during the last years? Do these have implications for treatment? How to treat relapse? Can treatment related late effects be mitigated?

We are honored to present Birgitta Lannering as the 2014 NOPHO Lecturer.

Birgitta Lannering, professor of Pediatric On-cology, was born in Uppsala, Sweden and re-ceived her medical degree from the University of Gothenburg in 1978, specialist in Pediatrics in 1983. She spent a year in Nashville in 1980 working with neonatology before entering the field of pediatric oncology.In 2000 she worked one year at Karolinska University Hospital with pediatric oncology. Birgitta has been deeply involved in brain tumors since the beginning of her career. She

was one of the founders of the Swedish group for brain tumors; VCTB as well as of the Nordic group for brain tumors. She has for long time been involved in the European group for brain tumors and has coordinated the international multicenter PNET-study. A few years ago she started the Swedish network for Neuroblas-tomas and CNS-tumors, NBCNS which has now grown to a strong research platform for neuronal tumors. She has been the Head of the Pediatric

Oncology Department in Gothenburg from 2006-2012. Birgitta is a talented singer and has demon-strated her excellent skills for impersonating a certain member of the Swedish Royal family at staff get-togethers. In Göteborg she is fa-mous for her German accent and also known as Queen Silvia. She likes spending time at her summer house by the coast and is a much val-ued colleague both at the department in Goth-enburg and within the whole NOPHO family.

NOPHO Lecture 2014

Photo: Bergen Tourist Board / Per Eide


O–01 A Nordic platform for clinical ethics in pediatric oncology

O–02 Treatment decisions in pediatric healthcare – Who’s the one to decide?

O–03 Hospital Admissions for Respiratory Disorders in Adult Life after Childhood Cancer in Scandinavia (ALiCCS) – A population-based cohort study www.aliccs.org

O–04 Diseases of renal function and bone metabolism following treatment of early-onset cancer. A registry-based study.

O–05 Hepatic Veno-Occlusive Disease in Children with Acute Lymphoblastic Leukemia During Maintenance Therapy with Continuous Asparaginase.

O–07 Intra-tumoral heterogeneity of T-ALL leukemic blasts at diagnosis and follow-up; implications for minimal residual disease detection

O–08 Genomic characterization of dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemia

O–09 RESPECT – A feasibility study of a school re-entry, physical- and social activity intervention for school children with cancer

O–10 Flow Cytometric Measurement Of Platelet Associated Immunoglobulin In Children With Newly Diagnosed Immune Thrombocytopenia

O–11 PPM1D/Wip1 is a novel neuroblastoma oncogene and potential therapeutic target in high-risk neuroblastoma

O–12 Paediatric germ cell tumors in Denmark, 1985–2012

O–13 Late mortality among Finnish 5-year survivors of early onset cancer

O–14 The SALUB registry: survivorship passport and nationwide registration of late-effects after childhood cancer in Sweden

O–15 Conceptual clarity of values in end-of-life deliberations in pediatric oncology

O–16 Incidence Of Thrombosis In Children Treated According To Non-Hr Nopho All 2008 – A Prospective Single Center Study

O–17 Hyperferritinemia in severely ill patients: associations with clinical and laboratory findings

O–18 Thalassemia and Diamond Blackfan Anemia in Sweden. Data from the Nordic Transfusion Registry

O–19 Iron deficiency and iron deficiency anaemia in toddlers in Oslo. Is there a difference between children of different ethnic backgrounds?

NOPHO / NOBOS

Annual Meeting9 – 13 May 2014 – Bergen – Norway

Overview

FREE PAPERS

ORAL PRESENTATIONS


O–01

A Nordic platform for clinical ethics in pediatric oncology

Pernille Wendtland Edslev, Aarhus University Hospital, pediatric Oncology, Denmark

IntroductionEthical problems in pediatric oncology have tradition-ally been handled at an individual level, and are often considered challenging. A joint working group on eth-ics, consisting of pediatric oncology nurses and physi-cians, was constituted during the NOPHO/NOBOS Annual Meeting in Linköping 2008. The intention of the working group is to be a Nordic competence group addressing ethical questions within pediatric oncology. By improving and sharing ethical knowledge, patient care and staff decisions may improve. Aim We pre-sent the activities and achievements of the NOPHO/NOBOS Working Group on Clinical Ethics (WGE) 2008-2013. Method The WGE has 14 members (7 nurses and 7 physicians) with at least two representa-tives from each of the Nordic countries. The group has met yearly at two meetings and one workshop. Meetings are organizational and educational with invited speakers. All members are educated through international courses and conferences in clinical ethics and are trained facilitators in moral case deliberation. Results All WGE members participate in, or have initiated, formalized clinical ethics projects at their pediatric departments, hospitals, regions or countries. Most clinical projects provide deliberation on ethically difficult cases on a regular basis as an integrated part

of daily work in pediatric oncology. Ten members are active in local clinical ethics committees. Two members have initiated or supervise research projects on ethical matters. Two members teach ethics to nurse or medi-cal students. One is a board member in a national society for clinical ethics. Conclusion It has proved beneficial to combine pediatric oncology nurses and physicians from different countries in a joint working group. Through collaboration and education we have created a common Nordic platform for developing clinically applied ethics. Importantly, the WGE has inspired and enabled all members to initiate or engage actively in projects locally, regionally and nationally, thus increasing the focus on clinical ethics.

Keywordsclinical ethics, moral case deliberation

Authors Trine Brøner1, Anders Castor2, Sigrún Þóroddsdóttir3, Pernille Wendtland Edslev1, Britt-Marie Frost4, Heidi Glosli5, Solveig Hafsteinsdóttir3, Hilde Frøland Hauge5, Kristian Juusola6, Satu Lehtinen6, Pernilla Pergert7, Gitte Petersen8, Astrid Sehested8 and Lisa Törnudd9, on behalf of the NOPHO/NOBOS Working Group on Clinical Ethics.

O–02

Treatment decisions in pediatric healthcare – Who’s the one to decide?

Lisa Törnudd, University Hospital of Linköping, Sweden, Pediatric Oncology, Sweden

Introduction In the field of pediatric healthcare the area of autonomy and self-determination vs. a joint decision, raises many questions. What say does a pediatric patient have in decisions regarding treatment that sometimes might be of life and death character? What say do the par-ents have? And who decides when a child is old and/or mature enough to make his/her own decisions? These dilemmas can be lifted in ethical consultations but they are also to some extent legally regulated. Aim The aim was to get a better understanding of the legal aspects of decision-making for children in our healthcare system and also to compare the legal status of children in the healthcare system in the different Nordic countries. Method A workshop was held by the WGE where legal expertise from Sweden, Norway, Finland and Denmark where invited to give lectures on the legal layout in the different countries and to give legal guidance in case discussions. Results An article on the basic legal rules applying to decision-making regarding minors and the differences between the countries was drafted. Conclusion Autonomy has a

central role in all of the four countries. When it comes to minors and their right to self-determination another important concept is maturity. Before a child is mature enough to be deemed capable of full self-determination the right and duty of decision-making is divided between the child, the parents and the physician. All countries have signed the UN Convention of Rights of the Child (CRC) stating that the best interest of the child should take first place. How much guidance the law gives the physician in assessing the maturity and ability to self-determination differs between the countries where the legislation in Sweden is vague, as it is in Finland while Denmark and especially Norway have more detailed laws.

Keywords Law, ethics, decision-making, pediatric

Authors Author: Lisa Törnudd and Britt-marie Frost on behalf of NOPHO/NOBOS Working Group on Ethics (WGE).

NOPHO Or al Presentation NOPHO Or al Presentation


O–03

Hospital Admissions for Respiratory Disorders in Adult Life after Childhood Cancer in Scandinavia (ALiCCS) – A population-based cohort study www.aliccs.org

Thorgerdur Gudmundsdottir, Danish Cancer Society Research Center, Survivorship Unit, Denmark

Background Pulmonary diseases are the second leading non-malignant cause of death among childhood cancer survivors. We therefore assessed the risk of hospitali-zation for respiratory disorders in Nordic childhood cancer survivors in a large population-based study. Material and methods First time hospitalizations for respiratory disorders were evaluated in a cohort of 29 247 one-year childhood cancer survivors and 196 222 population comparisons from the five Nordic countries. The nationwide cancer registries, central population registries and hospital registries were used to identify cohort members and their hospitalizations. Survivors were diagnosed with cancer below age 20 and recruited from the beginning of cancer registration in the 1940s and 1950s through 2008. Cohort members were followed individually for diagnoses for respiratory disorders through register linkages. Absolute excess risk (AER) per 100 000 person-years and standard-ized hospitalization rate ratios (RR) were calculated with corresponding 95% CIs. Results Survivors had a two-fold increased risk of a first time hospitalization for any respiratory disorder (n=5271; RR=2.2; 95% CI 2.1–2.2; AER=700). The risk persisted throughout life with a cumulative risk >60% >60 years of age. The highest risk was seen for radiation pneumonitis (n=24; RR=189; 26–1266), respiratory failure (n=184;

RR=6.4; 5.3–7.8), pleural effusion (n=160; RR=6.5; 5.3–8.0), pneumonia (n=1901; RR=5.2; 4.9–5.5), and acute upper respiratory tract infections (n=1945; RR=2.7; 2.6–2.8). However, pulmonary fibrosis (n=3; RR=4.2; 1.0–16.8) was registered less frequently than in previous reports. Survivors of leukaemia (RR=3.7) and Hodgkin lymphoma (RR=2.6) had the highest risk of respiratory disorders while survivors of retinoblastoma had the lowest risk (RR=1.0). Conclusions Survivors of childhood cancer are at an increased risk for respira-tory disorders compared with the general population. Awareness of this excess risk is important for clinicians and the growing survivor population; and essential for optimizing patient counselling and follow-up.

Keywords Childhood cancer survivorship, late effects, respira-tory disorders, hospitalizations, clinical epidemiology

Authors Thorgerdur Gudmundsdottir, MD, Jeanette Falck Winther, MD, DMSc, Sofie de Fine Licht MSc, Trine Gade Bonnesen, MD, Peter Haubjerg Asdahl, MD, Laufey Tryggvadottir, MSc, Harald Anderson, PhD, Finn Wesenberg, PhD, Nea Malila, PhD, Henrik Hasle, Professor, MD, PhD, Jørgen H Olsen, MD, DMSc, on behalf of the ALiCCS study group.

O–04

Diseases of renal function and bone metabolism following treatment of early-onset cancer. A registry-based study.

Marika Grönroos, Turku University Hospital, Pediatrics, Finland

BackgroundConstant progress in cancer therapy has led to a growing number of early-onset cancer survivors who are prone to increased morbidity owing to the late-effects of their anticancer therapy. The aim of this study was to investigate pediatric and young adult cancer survivors’ morbidity on renal diseases and on diseases of bone metabolism in a registry setting in a population-based level. The patient cohort was identi-fied from the Finnish Cancer Registry, and consisted of 13,860 5-year-survivors of cancer diagnosed below the age of 35. Their siblings without early-onset cancer were identified from the central population register and were used as the control cohort. Information on their morbidity on renal diseases and on diseases of bone metabolism was collected from the national hospital discharge registry and was used to assess hazard ratios for various outcomes. The patient cohort was separated into two age groups, pediatric (age at cancer diagnosis 0-19 years) and young adults (age at cancer diagnosis 20-34 years). Significantly elevated hazard ratios compared to the controls were observed in the following outcomes: scoliosis HR 1,6 (95% CI 1,3-2,0),

osteoporosis HR 5,2 (95% CI 2,4-11,4), osteonecrosis HR 12,7 (95% CI 5,4-29,7), nephritis HR 1,9 (95% CI 1,5-2,2) and kidney failure HR 3,6 (95% CI 2,4-5,3), p<0,0001 for all. All of the mentioned hazard ratios were significantly elevated in both diagnostic age groups. The hazard ratio for obesity was elevated in the pediatric age group for females HR 3,4 (95% CI 1,6-7,2) and for all survivors of CNS tumors HR 2,8 (95% CI 1,4-5,7). Survivors of pediatric and young-adult cancers are at increased risk for several long term adverse outcomes, and this must be taken into account in their follow-up. Our study provides new population-based information on the early-onset cancer survivors’ morbidity on renal diseases and on diseases of bone metabolism.

Keywords cancer survivors, late-effects, obesity, renal failure, osteoporosis

Authors Marika Grönroos Niilo Liuhto Nea Malila Laura Madanat-Harjuoja Jaakko Matomäki Päivi Lähteenmäki



O–05

Hepatic Veno-Occlusive Disease in Children with Acute Lymphoblastic Leukemia During Maintenance Therapy with Continuous Asparaginase.

Silvia De Pietri, University Hospital Rigshospitalet, Department of Pediatrics and Adolescent Medicine, Denmark

Introduction: Hepatic veno-occlusive disease (VOD) is a severe toxic liver-syndrome occurring in relation to chemotherapy exposure. Outside the transplantation setting, VOD in children with acute lymphoblastic leukemia (ALL) has been primarily associated with oral 6-thioguanine (6TG) administration. Nevertheless we observe an increased incidence of VOD during maintenance therapy with 6-mercaptopurine (6MP). In this ret-rospective case-control study we describe VOD cases occurring during non-high risk treatment. Method: among children treated in Rigshospitalet according to NOPHO-ALL 2008 under standard/intermediate risk regimen, only the ones assigned to continuous asparaginase therapy were included (n=42). VOD was defined by presence of at least 2 of three core features and no other explanation for liver impairment; 1) hyperbilirubinemia, 2) hepatomegaly and/or right-upper quadrant pain, 3) ascites and/or unexplained weight gain (>2,5% from baseline). Results: 9 patients (21,4 %) met the criteria for VOD (3 IR and 6 SR). 4 (2 SR and 2 IR) experienced a second (or third) VOD episode. Total number of VOD episodes: 16. All events occurred in Maintenance-I during continu-ous asparaginase. Median time-points for first VOD: week 4 (2-7) and week 7 (3-7) of Maintenance-I for SR and IR, respectively. VOD incidence was 30%

(9/30) after excluding patients who did not receive any PEG-asparaginase during Maintenance-I due to prior side effects. Clinical presentation at diagnose: hyperbilirubinemia (n=16) with mean value 104 µmol/l (=6x UNL, SD 52), rapid weight gain >2,5 % (n=9), diffuse abdominal pain (n=9), right-upper quadrant pain (n=3), ultrasound-verified ascites (n=4), ultrasound-verified hepatomegaly (n=1), reduced portal vein flow (n=1). Discussion: Diagnosis of VOD is challenged by the lack of objective and spe-cific parameters developed for non-transplanted ALL patients. The high incidence underlines the need for further investigations on pathogenetic factors. We will prospectively investigate 6MP metabolism under continuous PEG-asparaginase therapy as a risk factor for VOD (results will be presented).

Keywords Childhood Acute Lymphoblastic Leukemia, Veno-Occlusive Disease, Maintenance therapy, Asparaginase, 6-Mercaptopurine.

Authors Silvia De Pietri (presenting author), Stine Nygaard Nielsen, Jacob Nersting, Thomas Leth Frandsen and Kjeld Schmiegelow.

O–07

Intra-tumoral heterogeneity of T-ALL leukemic blasts at diagnosis and follow-up; implications for minimal residual disease detection

Nina Friesgaard Øbro, Copenhagen University Hospital, Rigshospitalet, Department of Clinical Immunology, Denmark

Background Heterogeneity of T-cell acute lymphoblastic leukemia (T-ALL) blasts may compromise MRD monitoring, the most important prognostic tool in T-ALL. PCR is currently used for MRD monitoring, but potentially both PCR-MRD and flow-MRD methods might miss blast subpopulations that differ from the dominating clone at diagnosis, which is important if subpopula-tions have divergent chemo-sensitivity. Methods: We investigated intra-tumoral heterogeneity of leukemia-associated immunophenotype (LAIP) by 8-color FC in diagnostic bone marrow (BM) samples from 49 T-ALL patients (NOPHO ALL-2008). 22 of these were also analyzed for diversity of TCR gene-rearrangements in flow-sorted blast subpopulations. MRD LAIP markers were evaluated by PCR TCR-marker detection in flow-sorted cells (61 early follow-up BM samples from 30 pts). Preliminary results: >80% of the T-ALL patients had at diagnosis heterogeneous LAIPs with bimodal marker expression, most often of CD1a, CD4, and TdT. Dominant TCR clonal gene rearrangements were generally conserved across the phenotypically diverse blasts, except in one patient. We did not detect any association between a high number blast subpopulations at diagnosis (>two markers bimodally expressed) and high MRD level (PCR-MRD d29 >0.1%). We observed antigen-specific LAIP changes during treatment (e.g.

loss of CD1a and TdT). The percentage of predicted LAIP-defined sorted MRD cells being PCR-positive was: 94% in pt. with fully informative LAIP and 76% in pt. with partly informative LAIPs (not all blasts having aberrant marker expression)). The percentage of cells classified as normal cells being PCR-negative when sorted was: 93-95% (in ptt. with informative LAIP) or 62-75% (in ptt. with partly informative LAIP). Summary: Intra-tumoral heterogeneity of immaturity and T-linage markers was common in T-ALL. The phenotypically diverse blasts generally had invariable TCR gene-rearrangements; accordingly PCR-MRD would detect all subpopulations. When all blast of heterogeneous LAIPs were informative, MRD identified by flow was highly concordant with cells positive for TCR MRD markers.

Keywords T-cell acute lymphoblastic leukemia (T-ALL); Intra-tumoral heterogeneity; Leukemic cell sub-populations; Minimal residual disease (MRD).

Authors Nina Friesgaard Øbro, Lars P. Ryder, Hans O. Madsen, Birgitte K. Albertsen, Peder S. Wehner, Steen Rosthøj, Nina Toft, Kjeld Schmiegelow, and Hanne V. Marquart. Presenting author: Nina Friesgaard Øbro



O–08

Genomic characterization of dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemia

Vasilios Zachariadis, Karolinska Institutet, Molecular Medicine and Surgery, Sweden

BackgroundThe chromosomal aberration dic(9;20)(p13.2;q11.2) occurs in up to 5 percent of pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). It is associ-ated with a poorer prognosis than the most common cytogenetic aberrations, such as t(12;21)(p13;q22) and high hyperdiploidy, and therefore patients with dic(9;20) are stratified to the intermediate risk treat-ment arm in the NOPHO ALL-2008 protocol. We have previously shown that in addition to the common, gross chromosomal rearrangement, dic(9;20)+ cases also share submicroscopic genomic losses and gains - including small, bi-allelic deletions of the tumor suppressor gene CDKN2A. Still, our understanding of the genetic basis of dic(9;20)-positive BCP ALL is limited. Some cases are thought to express fusion transcripts as a result of the dicentric rearrangement, which may produce chimeric proteins influencing leukemic development. Previous studies are, however, all limited in resolution and number of cases included. Here we present the genomic characterization of 25 dic(9;20)(p13.2;q11.2) BCP ALL cases. To understand the full spectrum of genomic lesions involved in developing and maintaining dic(9;20)+ leukemia, we examined diagnostic samples using high resolution single nucleotide polymorphism microarrays (Illumina Omni 2.5M), DNA methylation arrays (Illumina Infinium 450k), and deep transcrip-

tome sequencing (total RNA-seq). Homozygous dele-tions of CDKN2A, encoding the tumor suppressors P16INK4 and P14ARF, were detected in all cases. In addition, deletions of IKZF1, encoding the lymphoid transcription factor Ikaros, were present in 40% of cases - a clear enrichment compared to other subtypes of BCP ALL. Transcriptome sequencing also revealed recurrent gene fusions involving PAX5, including the in-frame fusion PAX5-C20orf112. With this study we expect to gain important new insights into the pathogenetic basis of dic(9;20)+ BCP ALL and, by integrating different modalities of genetic information, reveal common signaling pathways available for future targeted therapies.

Keywords dic(9;20), BCP ALL, transcriptome sequencing, fusion genes

Authors Vasilios Zachariadis (presenting author) Jessica Nordlund Ingegerd Öfverholm Johan Dahlberg NOPHO representatives* Magnus Nordenskjöld Gudmar Lönnerholm Erik Forestier Gisela Barbany Ann-Christine Syvänen Ann Nordgren (*NOPHO representatives of centers with cases enrolled in final study cohort)

O–09

RESPECT – A feasibility study of a school re-entry, physical- and social activity intervention for school children with cancer

Anne Sofie Helms, University Hospital Rigshospitalet , Pediatrics and Adolescent Medicine , Denmark

Background During cancer treatment children have reduced con-tact with their social network of friends, including participation in education, sports and leisure activi-ties. During and following cancer treatment children describe school related problems, reduced physical fitness and social problems. Purpose: Ensure children’s level of education, physical fitness and age appropriate everyday-life and to enhance quality of life. Primary endpoints: One year after first-line cancer therapy; a) level of educational achievement, b) level of VO2-max. Secondary endpoints: a) quality of life, b) physical performance. Patients/methods: RESPECT study is a nationwide prospective controlled intervention study addressing children newly diagnosed with can-cer (6-18 years) in eastern Denmark (N = 120) and a matched control group in western Denmark (N = 120). Intervention program: • An educational program on cancer aimed at the classmates. • Assignment of two ambassadors (classmates), who biweekly visit the child and participate in the intervention program. • Academic education program developed by the teachers followed by children and ambassadors at the hospital. • Individual and biweekly group based physical activity training. Measure: Diagnosis, three and six months after diagnosis, and one year after cessation of treat-

ment. Methods: Validated questionnaires, physical performance test, DNA profile, Dexa-scan, qualita-tive interviews and observational study. Preliminary RESULTS: 33 children with cancer are included in the intervention group. All schools have accepted the cancer education program (100%), all children have ambassadors (100%). It is possible to ensure safe trans-portation (1-350km), and achieve a biweekly visit rate during treatment. Conclusion: The study is powered to quantify the impact of a combined educational, physical and social intervention program. It is the first population-based study to examine the effect of early rehabilitation and to use healthy classmates as ambassadors to facilitate normalization of social life at the hospital and contributes with knowledge on rehabilitation that can facilitate rehabilitation of other long-term hospitalized children.

Keywords childhood cancer, school re-entry, intervention, peers, physical activity

Authors Helms, Anne Sofie (presenting author) Schmiegelow, Kjeld Larsen, Hanne Bækgaard Thorsteinsson, Troels



O–10

Flow Cytometric Measurement Of Platelet Associated Immunoglobulin In Children With Newly Diagnosed Immune Thrombocytopenia

Ole Haubjerg Nielsen, Aalborg University Hospital, Pediatrics, Denmark

Background Immune thrombocytopenia (ITP) is an immune medi-ated disorder, but attempts to develop a useful direct antiglobulin test have been unsuccessful. We have used flow cytometry (FCM) to measure platelet associated immunoglobulin (PAIG) at the time of diagnosis and here review the clinical utility. Methods: Since 1993, PAIG has been measured within 15 days of diagnosis and before any treatment in 68 of 88 children with newly diagnosed ITP. Using fluorescent murine anti-IgM and IgG, the amount of platelet bound antibody was graded on a semiquantitative scale from 0 to 3. The results have been related to clinical manifestations and clinical course. Results: PAIG was elevated (grade 1-3) in 74%. IgM elevation was found in 63%, IgG elevation in 46%. Raised PAIG was most frequent in children with insidious symptom onset (89%), less frequent in those with postinfectious (73%) or acute (59%) onset. An isotype shift to IgG from IgM was seen in the three groups. PAIG-positive cases had very low platelet counts (< 5/nL) and mucosal bleeding more frequently than PAIG-negative cases at the time

of diagnosis. Clinically significant bleeding episodes during subsequent follow-up also were more frequent in positive cases (18% vs. 6%), but there was no relation to duration of thrombocytopenia. The isotype profile, on the other hand, appeared to be predictive: elevation of both IgM and IgG was associated with duration <3 months (19 of 23). Conclusion: FCM measurement of PAIG can be performed easily and rapidly. The result may provide some prognostic information. One quar-ter of children are PAIG-negative and have mild and “dry” ITP with an uneventful course. PAIG-positive children with elevation of both isotypes usually have early spontaneous platelet recovery. The impact of raised PAIG on platelet function needs to be investigated.

Keywords Platelet associated immunoglobulin, immune throm-bocytopenia, ITP, flow cytometry

Authors Ole Haubjerg Nielsen, Ruta Tuckuviene, Kaspar Rene Nielsen, Kim Varming & Steen Rosthøj

O–11

PPM1D/Wip1 is a novel neuroblastoma oncogene and potential therapeutic target in high-risk neuroblastoma

Jelena Milosevic, Karolinska Institutet, Women’s and children’s health, Kvinnors och barns hälsa, Sweden

Background In neuroblastoma gain of 17q is the most powerful genetic predictor of adverse clinical outcome. 17q+ correlates with poor survival in our population-based material where we found aberrations of chromosome 17 in 85% of primary neuroblastomas, specifically, gain of PPM1D/Wip1 at 17q23. Wip1 is a serine/threonine phosphatase encoded by the gene PPM1D, described as a gatekeeper in the Mdm2-p53 regulatory loop involved in genetic stability, inflammation and a potential oncogene contributing to carcinogenesis. Methods: Comparative genomic hybridization (CGH), immunostaining, mRNA arrays, qPCR, exome- and RNA-sequencing was used to examine PPM1D/Wip1 in neuroblastoma. Genetical and pharmacological inhibition was used to analyse the function of Wip1 in preclinical neuroblastoma models. Results: CGH-array analysis detected PPM1D/Wip1 extra copies in all tumors and cell lines containing 17q-gain. Expression arrays and immunostaining showed high expression of Wip1 in neuroblastoma corresponding to poor survival. RNA-sequencing confirmed PPM1D-gain and revealed truncated isoforms with oncogenic potential. Exome-sequencing detected a mutation leading to constitutive PPM1D/Wip1 activation in an aggressive metastatic infant neuroblastoma. Wip1 knockdown experiments showed significant decrease of cell viability, proliferation and colony formation as well as substantial increase

of DNA-damage response in neuroblastoma cells. Tumor xenograft development was significantly delayed showing median tumor development (0.10 mL) to be more than doubled (median 15 days, vs. 33 days, p<0.001) after Wip1 downregulation compared to scrambled controls. A novel Wip1 inhibitor was highly potent in cytotoxic/cytostatic effect in neuroblastoma cell lines (median IC50 0.8 µM). Furthermore, this Wip1 inhibitor significantly inhibited growth of established human neuroblastomas in nude mice after 12 days of treatment (P<0.01). Tumor volumes were reduced 56% compared with controls after treatment. Conclusions: Our results show that PPM1D/Wip1 is oncogenic in neuroblastoma development activated due to chromosomal gain, alternative RNA-isoforms and/or DNA-mutation. PPM1D/Wip1 provides a novel therapeutic target in high-risk neuroblastoma.

Keywords Neuroblastoma, PPM1D/Wip1, oncogene, DNA-repair, Carcinogenesis

Authors Jelena Milosevic, Diana Treis, Malin Wickström, Susanne Fransson, Hjalmar Ståhlberg Nordegren, Baldur Sveinbjörnsson, Ninib Baryawno, Santhilal Subhash, Chandrasekhar Kanduri, Tommy Martinsson, Kazuyasu Sakaguchi, John Inge Johnsen, Per Kogner



O–12

Paediatric germ cell tumors in Denmark, 1985–2012

Madeline Evers, Rigshospitalet, Cph University Hospital, Hematology and Oncology Pediatric department, Denmark

Background/Purpose Germ cell tumors (GCTs) are a heterogeneous group of tumors derived from primordial germ cells. GCTs are benigne or malignant tumors localized either gonadal or extragonadal. We mapped the Danish paediatric cohort of GCTs and extracted data on localization, gender, histology, tumor markers and treatment. Methods All Danish paediatric GCTs in 1985-2012 were collected from the Danish Children Cancer Registry and case records were reviewed. Our preliminary results con-cern patients from one of the four centers who were treated at Rigshospitalet, Copenhagen University Rigshospitalet (area population approx. 2,5 mill). Results for the whole country will be presented at the meeting. Results We identified 120 GCTs (45% gonadal) in patients aged 0-15 years (crude incidence: 1,5/100.000, 67% girls). Overall mature teratomas were the most observed histological classification (57%) and usually localized in the ovaries. Extragonadal GCTs were mainly observed in early childhood (76%) with sacrococcygeal localization as the most common. In contrast, gonadal GCTs were observed in late child-

hood (59%) with ovaries as the most frequent site of origin. Serum AFP was elevated in 15% and only 4% showed elevated HCG. Approximately one third (37 children) of the GCTs were malignant. Of these, 50% were treated with chemotherapy. Almost all cases had surgery. Only 1 patient died and a few had severe morbidity. Conclusions In Denmark paediatric GCTs are rare and are mainly benign with mature teratoma being the most frequent. We identified a peak of extragonadal GCTs in early childhood and a peak of gonadal GCTs in late childhood. In malignant GCTs mortality/morbidity is very low but chemotherapy is administered for half the patients.

Keywords Germ Cell Tumors, benigne, malignant, Denmark, paediatric

Authors Madeline Evers, Jesper Brok, Catherine Rechnitzer Presenting author: Madeline Evers

O–13

Late mortality among Finnish 5-year survivors of early onset cancer

Päivi Lähteenmäki, Turku University Hopital, Pediatrics, Finland

Background Increasing survival rates have been reported especially for childhood cancer patients after 1970. Up to date, only few studies are available concerning the late mortality among early onset cancer survivors, espe-cially regarding young adulthood (YA) malignancies. Methods: Our nation-wide population-based registry study provides information concerning cause-specific long-term mortality up to year 2012 among 16,769 5-year survivors of early onset cancer (aged 0-34 years at diagnosis). A sibling cohort in addition to population data was used as reference. Results: Compared with population data, the overall standardized mortality ratio (SMR) of cancer patients was 4.6-fold, (95% CI 4.4-4.8). The SMRs were highest for malignancies (12.8, 95% CI 12.3-13.3), followed by infectious (4.8, 95%CI 2.9-6.7) and cardio-vascular diseases (1.9, 95% CI 1.7-2.1). Malignancies and cardiovascular diseases accounted for largest death numbers. Same primary cancer diagnosis for childhood and YA cancer survivors displayed elevated overall SMRs at the same range, with the exception of markedly higher values after childhood Hodgkin lymphoma (HL). Moreover, childhood central nervous system (CNS)-tumor, HL and non-Hodgkin lymphoma (NHL) survivors were predisposed to higher SMRs due to cardiovascular

causes than survivors of corresponding YA malignan-cies . The highest cumulative non-malignancy-related mortality was due to cardiovascular disease with a steady rise throughout the follow-up, but strongly dependent on the primary cancer diagnosis and age at diagnosis. Different from survivors of YA malignancies, no reduction of cumulative cardiovascular mortality was observed in childhood cancer survivors towards the recent treatment periods.. However, overall and malignancy-related mortality showed declining pro-portions towards the most recent periods after both, childhood and YA cancer. Conclusion: Our findings on non-malignancy-related mortality stress the need to set up long-term individual follow-up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lack-ing those.

Keywords cancer, child, late mortality, young adult

Authors Andreina Kero, Liisa Järvelä, Mikko Arola, Nea Malila, Laura-Maria Madanat-Harjuoja, Jaakko Matomäki, Päivi M. Lähteenmäki The presenting author: Päivi Lähteenmäki.



O–14

The SALUB registry: survivorship passport and nationwide registration of late-effects after childhood cancer in Sweden

Cecilia Petersen, Karolinska Institutet, Women’s and Children’s Health, Sweden

BackgroundThe Swedish working group for long-term follow-up after childhood cancer (SALUB) has developed an extension of the on-line based Swedish Childhood Cancer Registry. Beside the purpose of a nationwide registration of late-effects, the aim was also to create a patient-friendly summary with recommendations for future follow-up. The SALUB-registry contains detailed treatment information on cumulative doses of traditional chemotherapy, other anti cancer drugs, radiotherapy doses towards targets and risk organs, surgery, central catheters and severe complications during treatment. The treatment data is separated into primary and relapse treatment with calculation of cumulative doses from all treatments. The health status at transition to adult care is reported in detail and relevant parts are transferred to the summary for the patient, the so-called survivorship passport. The passport contains recommendations on future follow-up and contact information to the physician responsible for the transition. The passport function is primarily based on free text, in order to personalize the informa-tion for the patient. The registry also contains an event

reporting form, aimed to be used in late-effect clinics. The SALUB-registry was launched in October 2012 and currently more than 400 patients are registered. The treatment data may be entered by a research nurse, but the health status and follow-up plan is signed by the physician responsible for transition. The SALUB-registry forms a basis for future research on long-term side effects of cancer treatment during childhood. It provides detailed health status information at the age of 18 and a survivorship passport for the patient. With the further development of late-effect clinics the registry can be used for prospective registration of late-effects during adult life, as well as retrospective studies of the approximately 7,000 former childhood cancer patients in Sweden now 18 years of age or older.

Keywords Late-effects, survivorship passport

Authors Cecilia Petersen, Omid Mavadati, Mats Heyman, Lars Hjorth on behalf of all SALUB members

O–15

Conceptual clarity of values in end-of-life deliberations in pediatric oncology

Anders Castor, pediatric oncology, pediatrics, sweden

BackgroundApproximately 20% of children with cancer die of their disease or the treatment. These deaths are often preceded by difficult decisions about continuation or abandonment of curative treatment when the prognosis is dubious. The challenges are partly medical, due to difficulties in determining the precise prognosis for each individual, available options might be supported by insufficient data, and/or the total situation might be highly complex. But in the discourse on what to do, these medical difficulties (as important as they are) must be clearly separated from the moral ques-tion “what should we do?” A major component of the moral question is the balancing of burdens and benefits for the patient. Morally important factors are values attached to the patient’s life, and can broadly be separated into questions of three different concepts of value: 1) sanctity, or inviolability, of the patient’s life (regardless of his or her own perception of it), 2) quality of life, and 3) dignity. These concepts represent distinct values, since a life with any two, but lacking the third, is conceivable. We would argue that these

notions sometimes, in thinking or discussing the ben-efit/burden balance in the individual case, might be confused by the decision maker. One interesting reason for this confusion is, that in the Nordic languages all three concepts (sanctity, quality, and dignity of life) can be, and often are, expressed by words containing the word value (värde, verdi, værdi, gildi), where the precise intended meaning is poorly defined. Because of this risk, we would recommend treatment teams to place special emphasis on clarification of these concepts, and question which value is intended, when deliberating treatment decisions. If they are not clear, the justification of the decision will not be either.

Keywords Decision-making, ethics, value, quality-of-life

Authors Anders Castor, Hilde Fröland Hauge, Heidi Glosli, Sigrún Þóroddsdóttir, Gitte Pedersen, on behalf of the NOPHO/NOBOS Working Group on Ethics



O–16

Incidence Of Thrombosis In Children Treated According To Non-Hr Nopho All 2008 – A Prospective Single Center Study

Ellen Ruud, Oslo University Hospital, Department of Pediatric medicine, Norway

Background Thrombosis is a complication to treatment of acute lymphoblastic leukemia (ALL), associated with cor-ticosteroid and asparaginase (ASP) administration. Objective: The aim was to study the incidence of symptomatic and asymptomatic thrombosis in children treated according to non-HR NOPHO ALL 2008 prospectively, and the association with asparaginase intensity (interval between injections), antithrombin (AT) activity and minimal residual disease (MRD). Method: We included 47 children (31 boys/16 girls) with median age 4 years (range 1.9–15.6 y). They were enrolled at protocol day 29 and observed for clinical relevant events until the last scheduled injection of ASP, 7 months later. Following the first 5 fortnightly scheduled doses of PEG-ASP after day 29, 18 children were further stratified to PEG-ASP every other week, 25 children every 6th week and 4 children had Erwinase®. We analyzed AT activity prior to ASP injections and performed ultrasonography of neck veins and lineogram (fluoroscopy of central line function) at protocol day 79 and around protocol week 35. Results: Five children

had symptomatic thrombosis (11%). Ultrasonography revealed neck vein thrombosis in 30/47 children (64%) and in 27/41 children (66%) at day 79 and at the last examination respectively. Study-lineograms showed catheter tip occlusion in 7/45 children (15%). Reduced AT activity (< 80%) was found in 35/45 children (78%) with median lowest activity 57% (range 18–111%). We observed MRD > 0.1% at day 29 in 6 children (13%). Persistent neck vein thrombosis was associated with MRD > 0.1% at day 29 (p = 0.02), but not associated with ASP intensity (p = 0.54) or lowest AT activity (p = 0.15). Symptomatic thrombosis was not significantly associated with any of the tested variables. Conclusion: In non-HR ALL-patients, the incidence of thrombosis is high and MRD > 0,1% at day 29 may be a prothrombotic risk factor. Keywords ALL, thrombosis, antithrombin, asparaginase, MRD Authors Ellen Ruud (presenting author), Målfrid Tveiterås, Kirsti Try, Charlotte de Lange

O–17

Hyperferritinemia in severely ill patients: associations with clinical and laboratory findings

Tatiana Greenwood, Karolinska Institiute, Childhood Cancer Research Unit, Dept of Women’s and Children’s Health, Sweden

BackgroundHyperferritinemia has been identified as an important biomarker of the genetic (primary) form of hemophago-cytic lymphohistiocytosis (HLH), a disease associated with excessive inflammation and characterized by defect lymphocyte cytotoxicity function. HLH may also develop in a secondary (acquired) form (sHLH), a potentially treatable hyperinflammatory condition that may be present in severely ill patients. Here we analyzed ferritin levels in patients at an intensive care unit (ICU) in order to correlate hyperferritinemia to clinical and other laboratory parameters in this group of severely ill patients. METHODS: Patients with ferritin levels >500 microg/L were prospectively studied at an ICU with regard to clinical and labora-tory features, including soluble CD25 (sCD25) and detailed lymphocyte cytotoxicity analyses in some, and subsequent genetic studies as appropriate. RESULTS: Hyperferritinemia and elevated sCD25, both markers of inflammation, were positively associated to each other in ICU patients with septicemia, a state of known excessive inflammation. At ICU admission, ferritin and sCD25 levels were inversely correlated to platelet counts in the total cohort and in patients with septicemia. Notably, thrombocytopenia is a sign

of severe illness that affects outcome and mortality of ICU patients. Hyperferritinemia was also associated with elevated CRP in septicemia patients. Elevated sCD25 was inversely correlated to hypoalbumine-mia in both groups. Interestingly, hyperferritinemia (>5,000 microg/L) was also associated with decreased cytotoxic function (10 LU). Notably, of four patients with abnormally low cytotoxic function, three (75%) had <5% circulating NK cells and one had a heterozy-gous variant in an HLH-causing gene (STXBP2). CONCLUSION: Our study suggests a correlation between hyperferritinemia and other laboratory values indicative of poor outcome in severely ill patients at intensive care units.

Keywords ferritin, hemophagocytic lymphohistiocytosis, hyper-ferritinemia, intensive care, septicemia

Authors Tatiana von Bahr Greenwood, Kajsa Palmkvist-Kaijser, Samuel C. C. Chiang, Terry Huang, Bianca Tesi, Eva Rudd, Magnus Nordenskjöld, Hans Hjelmqvist, Yenan T. Bryceson, and Jan-Inge Henter



O–18

Thalassemia and Diamond Blackfan Anemia in Sweden. Data from the Nordic Transfusion Registry

Ulf Tedgård, Dept of Pediatrics, Sweden

BackgroundChildren with transfusion dependent anemia’s (TDA) are at risk for severe complications due to iron overload affecting many organs, particularly the heart, liver and endocrine function. Good knowledge of iron chelation therapy, how it is followed and high patient compliance are important for event free survival. The number of patients in the Nordic countries with TDA is increas-ing and the Nordic blood transfusion registry (NTR) was initiated with the aim to improve awareness and knowledge of TDA treatment and its side effects. The NTR is a new NOPHO registry that is approved as a quality registry by Sveriges Kommuner och Landsting (SKL). In the NTR demographic, disease specific, treatment related data are registered as well as quality of life (QoL) and other patient reported outcome measurers. This study is a pilot testing of the registry for all patients up to 18 years of age in Sweden with transfusion dependent Thalassemia and Diamond Blackfan anemia. The above mentioned variables will

be presented. One aim of the study is also two compare two QoL questionnaires (Disabkids and PedsQL) and to find out which is preferred by the patients and which gives most relevant information. The results of these data will be important in order to improve patient care for these rare diseases.

Keywords Thalassemia, Diamond Blackfan anemia, children, registry, quality of life

Authors Anne Sjögren and Ulf Tedgård on behalf of the NOPHO Red Cell Disorders Working Group (Birgitte Lausen, Niels Clausen, Pernille Wendtland Edslev, Kirsi Jahnukainen, Kirsti Sirkiä, Island Olafur G. Jónsson, Marit Hellebostad, Anne Grete Bechensteen, Einar Stensvold, Göran Elinder, Jan-Inge Henter, Rolf Ljung, Magnus Göransson, Mimi Kjærsgaard, Nadine Gretenkort, Tina Lund Leunbach, Niina Valtanen)

O–19

Iron deficiency and iron deficiency anaemia in toddlers in Oslo. Is there a difference between children of different ethnic backgrounds?

Einar Stensvold, Oslo University Hospital, Department of pediatrics, Norway

BackgroundThe aim of the study was to compare the prevalence of iron deficiency (ID) and iron deficiency anaemia (IDA) in children of non-European origin with chil-dren of European ethnicity. In addition we wanted to demonstrate the benefit of including MCV and soluble transferrin receptor (sTfR) in the test panel when screening for ID and IDA, in addition to hae-moglobin and ferritin. The patients were included from the routine health-screening program for one-year-old children. In the study 172 children were examined, 73 girls (42.4 %) and 99 boys (57.6 %). 76 children were European (44 %), 96 were non-European (56 %). We found that 11 children (6.4 %) had ID. Four of these were European (2.3 %), seven were non-European (4.1 %). Mean Hb values did not differ, (11.7 (0.8) vs. 11.9 (0.9)) between the children of different ethnic background. There were however significant (p < 0.05) lower values for several iron parameters (like sTfR, MCV, reticulocytes, Ret-Hb and TIBC) in the non-European group, but ferritin did not differ between the groups. We identified a total of 7 haemoglobi-

nopathies (7.6 %); all of these had microcytosis, and were of non-European origin. When screening for ID using MCV, an overt microcytosis might indicate ID and a child at risk for developing anaemia, even with normal ferritin levels. Children with non-European background are more at risk of developing ID and IDA. With increasing non-European immigration to Norway, however, it is important to have in mind that children with microcytosis, not necessarily have ID, but might suffer from haemoglobinopathies Thus, when screening for ID and IDA in young children in Norway at health centres, we will recommend using a combination of Hb, MCV, and sTfR. With microcytosis and normal levels of sTfR, haemoglobin sub-typing analyses should be performed.

Keywords Anaemia, ethnic groups, iron deficiency, iron status

Authors Einar Stensvold, Anne Grete Bechensteen, Knut Liestøl, Petter Urdal and Marit Hellebostad.



P–01 Hospitalizations for Gastrointestinal Disease in Adult Life After Childhood Cancer in Scandina-via: a Population-based Cohort Study

P–02 Late morbidity in Finnish long-term survivors of childhood brain tumors

P–03 Military Service in Male Survivors of Childhood

Brain and Solid Tumors

P–04 Is there a need for clinical pharmacist in the pediatric oncology ward?

P–05 Premature Arterial Aging in Long Term Survi-

vors of High Risk Neuroblastoma Treated with TBI

P–06 The influence of TPMT polymorphisms on mini-

mal residual disease after 6-mercaptopurine consolidation therapy of childhood acute lymph-oblastic leukemia.

P–07 Increased frequency of cancer in female rela-tives of patients with primary defects in lym-phocyte cytotoxicity

P–08 Acute and late effects after radiotherapy – data

from RADTOX registry P–09 Extramedullary Leukaemia in Children With

Acute Myeloid Leukaemia P–10 Clinical characteristics and outcome in children

with hereditary spherocytosis: A single center observational study in 35 consecutive

P–11 Immunosuppressed children and respiratory

viral infections – A prospective follow-up study P–12 Case report of four patients with diffuse pon-

tine glioma. P–13 Interleukin-7 levels in plasma predict the rate

of T cell immune reconstitution in allogeneic stem cell transplantation

P–14 Exosomes from MYCN-amplified neuroblas-toma cells contain oncogenic microRNAs

P–15 Trisomy 8 in pediatric acute myeloid leukemia; a NOPHO-AML study

P–16 Thromboembolism in children with acute

lymphoblastic leukemia in the Nordic countries P–17 Medullary Thyroid Carcinoma in children with

MEN 2B in Norway. Clinical course of an or-phan disease.

P–18 Role of minor ALL-subclones carrying IKZF1

deletions in the development of relapse. P–19 6-Thioguanine and 6-Mercaptopurine Com-

bination Maintenance Therapy of a Girl with pre-B ALL

P–20 Early human germ cell development. P–21 Organ culture of rodent testicular tissue – Op-

timization of fertility preservation strategies.

P–22 Effect of basic culture media. – Do the storage and media per se affect testicular tissue?

P–23 Antibiotics Prior to Insertion of Central Venous

Catheters does not prevent Bacteremia in Chil-dren with ALL

P–24 Self-perception and self-esteem consequences

of CNS malignancy and brain tumour treat-ment in childhood/adolescence: Population-based survivor and general population out-comes compared

P–25 Assessment Of Transfusion Burden With Erythro-

cyte Concentrates In Children Treated For Acute Lymphoblastic Leukemia According To Nopho All-2008 Protocol

P–26 JMML with germlineCBL mutation in 1 year old

girl, succesful outcome without treatment. P–27 Intercranial Hemorrhage in Children with Im-

mune ThrombocytoPenia (ITP)

Overview

FREE PAPERS

POSTER PRESENTATIONS

NOPHO / NOBOS



P–01

Hospitalizations for Gastrointestinal Disease in Adult Life After Childhood Cancer in Scandinavia: a Population-based Cohort Study

Peter H. Asdahl, Aarhus University Hospital, Department of Pediatrics, Denmark

BackgroundIn the growing population of childhood cancer survivors, many late-onset treatment-related health consequences have been documented but little is known about gastrointestinal diseases. The objective of this study was to give a comprehensive and detailed overview of all gastrointestinal late effects in childhood cancer survivors. Methods Adult Life After Childhood Cancer in Scandinavia (aliccs.org) is an inter-Nordic collaboration investigating late effects of childhood cancer therapy. From the cancer registries in the Nordic countries, we identified all patients diagnosed with cancer under the age of 20 in the last six decades. We used population-based registries to obtain information on hospital admissions and deaths. For each one-year survivor we randomly selected five population com-parison subjects. Result The 31,132 one-year survivors had a total of 3,824 first time hospitalizations for gastrointestinal disease. The standardized hospitaliza-tion rate ratio (RR) for any gastrointestinal disease was 1.6 (95% Confidence Interval (CI): 1.6–1.7) and the absolute excess risk (AER) was 360 (95% CI: 330–390) extra hospitalizations per 100,000 person-years. Of six diagnostic groups, liver diseases had the highest RR (2.8 (95% CI: 2.5–3.1)) and intestinal diseases had the highest AER (220 (95% CI: 190–240)). Survivors of hepatic tumors, neuroblastoma, and leukemia had

the highest risk of hospitalization for gastrointestinal disease. Notably, we found increased risk for a number of serious specific diseases, e.g. esophageal strictures (RR: 13 (95% CI: 9.2–20), paralytic ileus (RR: 6.6 (95% CI: 5.7–7.5), acute and chronic pancreatitis combined (SHRR: 1.9 (95% CI: 1.6–2.3), and liver cirrhosis (SHRR: 2.9 (95% CI: 2.0–4.1). Among these, paralytic ileus had the highest AER (75 (95% CI: 66–84)). Conclusion Survivors of childhood cancer are at an increased risk of gastrointestinal diseases. The risk of certain serious specific diseases was increased but incidence remained low.

Keywords survivorship, late effects, gastrointestinal diseases, liver diseases, clinical epidemiology

AuthorsPeter H. Asdahl, MD, Jeanette F. Winther, MD, PhD, DMSc, Trine G. Bonnesen, MD, Sofie De Fine Licht, MSc, Thorgerdur Gudmundsdottir, MD, Jens F. Dahlerup, MD, DMSc, Laufey Tryggvadottir, MSc, Harald Anderson, MD, PhD, Finn Wesenberg, MD, PhD, Nea Malila, MD, PhD, Jørgen H. Olsen, MD, DMSc, Henrik Hasle, MD, PhD, on behalf of the ALiCCS study group.

P–02

Late morbidity in Finnish long-term survivors of childhood brain tumors

Päivi Lähteenmäki, Turku University Hospital, Pediatrics, Finland

Background The population of long-term survivors of childhood brain tumors is growing. Survivors¡¯ follow-up should be organized in a structured way. Most of the earlier research on the morbidity of this patient group has suffered from small sample sizes. On the other hand, studies with large sample sizes are based on self-reporting with a possibility for recall and selection bias. Methods: All brain tumor patients diagnosed with a neuroepithelial brain tumor at age 0-15 years in Finland between 1970 and 2004 were identified from the Finnish Cancer Registry and their late morbidity (¡Ý5 years after cancer diagnosis) was assessed using the Hospital Discharge Registry containing data on hospitalizations and outpatient visits in specialist health care. Results: The 5-year survivors of childhood brain tumors had a significantly increased hazard ratio for endocrine diseases (HR 14.7), mental and behavioral disorders (HR 1.8), mental retardation/disorders of psychological development (HR 16,6), diseases of the nervous system (HR 9.8), disorders of vision

and hearing (HR 10.5), and diseases of the circula-tory system (2.7) compared with the sibling control group. Most of the outcomes also had an increasing prevalence up to 10 to 30 years after primary diagnosis. The irradiated survivors had significantly increased HR compared with the survivors with no history of irradiation for endocrine diseases (HR 6.2), diseases of nervous system (HR 1.8) and disorders of vision or hearing (HR 2.1), but not for other main outcomes studied. Conclusions: Systematic long term follow-up and supportive measures are essential due to numerous late effects among childhood brain tumor survivors.

Keywords brain tumor, childhood, survivor, outcome, morbidity

Authors Erika Gunn, Tuire Lähdesmäki, Nea Malila, Mikko Arola, Marika Grönroos, Jaakko Matomäki, Päivi M. Lähteenmäki The presenting author: Päivi Lähteenmäki

NOPHO Poster Presentation NOPHO Poster Presentation


P–03

Military Service in Male Survivors of Childhood Brain and Solid Tumors

Päivi Lähteenmäki, Turku University Hospital, Pediatrics, Finland

BackgroundChildhood cancer and its treatment may cause multiple limitations on physical, neurocognitive and social functions of survivors. During military service, physical performance is tested into extreme, and good cognitive and social capacity are needed in order to manage the training. The aim of this study was to examine the acceptance of childhood solid and brain tumor survivors to the still mandatory military service in Finland, how the conscripts perform in the physi-cal and cognitive tests during the service, and what is the level of military education in childhood cancer survivors compared to controls without a cancer his-tory. Male cancer (below age 16 yrs) survivors that were born from 1960 to 1992, and alive at the age of 18 years (call-up age) (N=1143) were identified from Finnish Cancer Registry. From the Population Registry Centre, five age, sex and place of residence matched controls were identified (N=5714). Information on call-up decisions and military service of the study subjects was collected from the databases of Finnish Defence Forces. Enlistment frequency was 55% in Hodgkin lymphoma, 35 % in brain tumors, 55 % in neuroblastoma, 13 % in malignant bone tumors, 56 % in soft tissue sarcomas, and 68 %in kidney tumors.

Treatment with irradiation (p<0.001) and older age at cancer diagnosis (p=0.04) affected the military fitness category. Interruption of service occurred to same extent in survivors and controls, and the level of military education did not differ between groups (p=0.83). On average, enlisted solid tumor survivors managed physical tests and training similarly as con-trols. Only performance in standing long jump test was worse (p=0.005). Solid tumor survivors managed well in cognitive tests compared with controls. Enlisted survivors of brain tumors had slightly poorer physical performance than controls (p= 0.05), both in Cooper running test (p= 0.011) and in general muscle strenght (p=0.023). Brain tumor survivors had a decline in all tested cognitive skills, and irradiation treatment did not explain the findings.

Keywords cancer, childhood, military service, performance, survivor Authors Ritva Ahomäki, Tiina Remes, Kai Parkkola, Jaakko Matomäki, Arja Harila-Saari, Päivi Lähteenmäki The presenting author: Päivi Lähteenmäki

P–04

Is there a need for clinical pharmacist in the pediatric oncology ward?

Ranaa El Edelbi, Kvalitet och ut, Sweden

BackgroundDrug treatment in pediatric patients is challenging mainly because the majority of available drugs have been developed and tested to be use in adults. Age-specific changes in pharmacokinetics and pharmaco-dynamics during growth make pediatric patients drug therapy challenging. Specific information concerning proper use including dosing in children are lacking resulting in that about 50 % of all drugs prescribed to children in Swedish hospitals are off-label (unlicensed) (1). A pharmacist on the ward contributing with their knowledge with the aim to improve patient drug therapy and safety is appreciated (2). The pharmacist on the ward can ensure safe, effective, and economic use of medicines by monitoring drug therapy, routines and processes as well as evaluation of pediatric drug information, drug interactions, effectiveness, recom-mendations, storage and costs. The pharmacist on the ward can futhermore contribute with education of patients/parents on medication use to improve com-pliance and ensure correct use (3,4). There is a need for a Clinical Pharmacist Group within NOPHO! I therefore suggest that such an expert group should

be started for all pharmacists working with pediatric oncology or have interests in the subject. References 1. Kimland E, Nydert P, Odlind V, Bottiger Y, Lindemalm S. Paediatric drug use with focus on off-label prescrip-tions at Swedish hospitals - a nationwide study. Acta Paediatrica. 2012; 101:772-8 2. Sanghera N, Chan PY, Khaki ZF, Planner C, Lee KK, Cranswick NE, et al. Interventions of hospital pharmacists in improv-ing drug therapy in children: a systematic literature review. Drug Safety. 2006; 29:1031-47 3. Alsultan MS, Mayet AY, Khurshid F, Al-Jedai AH. Hospital pharmacy practice in Saudi Arabia: Drug monitoring and patient education in the Riyadh region. Saudi Pharm Journal. 2013; 21:361-70 4. Kaboli PJ, Hoth AB, McClimon BJ, Schnipper JL. Clinical pharmacists and inpatient medical care: a systematic review. Arch Intern Med. 2006; 166:955-64

Keywords Clinical pharmacist, oncology ward, patient safety

Authors Ranaa El Edelbi M sc Pharm, Staffan Eksborg Professor



P–05

Premature Arterial Aging in Long Term Survivors of High Risk Neuroblastoma Treated with TBI

Anu Vatanen, Children’s Hospital, Helsinki University Hospital, Division of Hematology- Onkology and Stem Cell Transplantation, 02100

Abstract Objective: The aim of the study was to evaluate arterial mor-phology and function among long term survivors of high risk neuroblastoma treated with hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Subjects and methods: Common carotid, femoral, brachial and radial artery morphology, carotid artery stiffness and brachial artery endothelial function were evaluated by ultrasound, fasting serum triglycerides and cholesterol measured, and 24h ambulatory blood pressure (BP) monitored in 19 adult or pubertal (age 22.7±4.9 years, range 16-30) survivors transplanted at Helsinki University Hospital during 1984-1999 at the mean age of 2.5±1 years, and compared with 20 age- and sex- matched healthy controls. Results: Survivors had consistently smaller arterial lumens, increased carotid intima-media thickness (IMT), plaque formation (N=3) and stiffness compared with controls. Survivors displayed higher

serum triglyceride and cholesterol levels, increased HR, and increased systolic and diastolic BPs. Multivariate analysis identified TBI and a low body surface area as independent predictors for decreased arterial lumen size, increased IMT and occurrence of plaque. Conclusions: High risk neuroblastoma survivors treated with TBI display significant signs of premature arterial aging during adolescence and young adulthood.

Keywords Cardiovascular Risk, Endothelial Function, High Risk Neuroblastoma, Late Effect, HSCT

Authors Vatanen Anu, Sarkola Taisto, Ojala Tiina H, Turanlahti Maila, Jahnukainen Timo, Pihkala-Saarinen Ulla M, Jahnukainen Kirsi Presenting author: Anu Vatanen, [email protected]

P–06

The influence of TPMT polymorphisms on minimal residual disease after 6-mercaptopurine consolidation therapy of childhood acute lymphoblastic leukemia.

Emilie Damgaard Brünner, University Hospital Rigshospitalet, Department of Pediatrics and Adolescent Medicine, Denmark

Background Minimal residual disease (MRD) measured after initial therapy is a potent prognostic factor for long-term outcome for children with acute lymphoblastic leukemia (ALL). During NOPHO ALL-2008 con-solidation therapy, patients receive 6-mercaptopurine (6-MP) in combination with HD-MTX. Thiopurine methyltransferase (TPMT) is a critical modifier of 6-MP pharmacokinetics/-dynamics. Low activity TPMT alleles are frequent and may enhance 6-MP treatment efficacy. Currently TPMT wild-type and TPMT heterozygous patients receive the same dose of 6-MP during this treatment phase. We explored the relationship between TPMT genotype and minimal residual disease (MRD) before and after 6-mercaptopurine based consolidation therapy accord-ing to the NOPHO ALL-2008 protocol. Eligibility: Patients treated according to the NOPHO ALL-2008 protocol and receiving fixed doses of 6-MP (25 mg/m2/day) during consolidation therapy. In total, 483 childhood B-precursor ALL patients were included. Method: Minimal residual disease was measured by flow cytometry on treatment day 29 and 79. TPMT genotype was analyzed by polymerase chain reaction (PCR). Results: We found no significant difference between the TPMT wild-type patients (N=433) and the TPMT heterozygous patients (N=48) with regard

to MRD levels on day 29 (P = 0.85) and day 79 (P = 0.34). The two genotype groups did not differ with regard to other characteristics known to be associated with treatment outcome such as age, sex, and white blood cell count at diagnosis. 39 patients had positive MRD (>10-4) on day 79. These patients did not differ significantly from the MRD negative patients with regard to the known prognostic variables, including TPMT genotype (P= 0.40). The actual median interval from protocol treatment day 29 to 79 was 54 (95% range: 47 - 80) and did not differ between TPMT wild type and TPMT heterozygous patients. Conclusions: TPMT genotype does not influence the MRD level after exposure to low doses of 6-MP during consoli-dation treatment according to NOPHO ALL-2008.

Keywords Childhood acute lymphoblastic leukemia, 6-mer-captopurine, minimal residual disease, thiopurine methyltransferase.

Authors Emilie Damgaard Brünner (presenting author), Louise Rold Helt, Jacob Nersting, Thomas Leth Frandsen, Jonas Abrahamsson, Finn Wesenberg, Mats Heyman, Olafur Gisli Jonsson, Goda Vaitkeviciene, Kaie Pruunsild, Kim Vettenranta and Kjeld Schmiegelow.



P–07

Increased frequency of cancer in female relatives of patients with primary defects in lymphocyte cytotoxicity

Alexandra Löfstedt, Karolinska Institutet, Department of women’s and children’s health, Sweden

BackgroundMutations in genes required for the perforin-dependent lymphocyte cytotoxicity are associated with early-onset hemophagocytic lymphohistiocytosis (HLH). Previous studies have demonstrated that individuals with hypo-morphic biallelic mutations in HLH-associated genes have an increased risk of developing hematological malignancies. In this study, we hypothesized that even relatives of primary HLH patients, i.e. heterozygous carriers of HLH-associated mutations, may display an increased risk of developing cancer. In an unbiased approach, we identified relatives of 79 Swedish primary HLH patients (diagnosed 1971-2011) using a multi-generation-registry. Cases as well as matched controls were cross-linked with the Swedish cancer registry. The overall cancer frequency and relative risk of cancer were established for the entire cohort, as well as separately for first- and second-degree relatives, and for women and men. Additionally, NK-cell-mediated cytotoxicity was assessed in a subgroup of first-degree relatives. A significantly increased frequency of malignancies was observed in first-degree relatives (parents; 12.8% compared to 7.2%, p=0.038). Remarkably, mothers accounted for the increased cancer frequency among

first-degree relatives (19.4% compared to 7.3%, RR=2.7; p=0.004) with cervical carcinomas as the most frequent cancer. Despite this finding, functional analysis of heterozygous carriers of HLH-associated mutations did not display significantly reduced lymphocyte cyto-toxicity as measured by current functional assays. In conclusion, the higher frequency of cancers in relatives of primary HLH patients indicates haploinsufficiency in female carriers for cytotoxic lymphocyte-mediated immunosurveillance of cancer. Our results signify the impact of mutations in genes required for lymphocyte cytotoxicity to human health and may speak in favor of intensified screening for malignancies in female relatives of primary HLH patients.

Keywords Hemophagocytic lympohistiocytosis, cancer suscep-tibility, malignancy, immunodeficiency, lymphocyte cytotoxicity

Authors Alexandra Löfstedt, Marie Meeths, Erik Onelöv, Sam C.C. Chiang, Yenan T. Bryceson, Jan-Inge Henter

P–08

Acute and late effects after radiotherapy – data from RADTOX registry

Kristina Nilsson, Uppsala University Hospital, Oncology, Sweden

Introduction: All children who have received radiotherapy (RT) after 2008 in Sweden are registered in a web based registry, RADTOX. The registry is based on the same information used by the German/Austrian/Swiss RiSK group registry, a group SvBRG have collaborated with since 2008. The aim of this study is to monitor the occurrence of grade 3 or grade 4 effects. Material and methods: The registry includes information about given RT and radiation dose data for most organs. In addition, we collect the complete DICOM data set for the treatment for future research. Acute and late side effects are documented on a RTOG/EORTC scale at end of RT, after 2 months and after 1, 3, 5 and 10 years after completing the radiotherapy. From Jan 2008 until Jan 2014 we have collected data for 484 patients from six Swedish radiotherapy centres. Follow-up data were available for approximately half of these children. The longest follow-up this far is five years. Results: At end of RT we scored 8% (11 of 132 reports) of the children with at least one grade 3 or 4 adverse effect. Two months after the end of the RT, 13 % (21 of 156) of the children suffer from one or

more adverse effects. After one to five years after RT, 11% (27 patients) are still affected by a grade 3 and/or 4 late effect. Most severe late problems arise from the upper GI (9 patients), followed by peripheral nerves (5), skin (4) eyes, ears, bone marrow (3 respectively) and CNS (brain) and joints (1 respectively). Conclusion: The adverse effects of the radiotherapy diminish over time, but many patients have serious side effect in long term follow-up. Dose relationships and contribution of side effects from surgery and chemotherapy will be further studied.

Keywords acute/late effects, pediatric radiotherapy

Authors Kristina Nilsson (Uppsala), Ingrid Kristensen (Lund), Anna-Maja Svärd (Umeå), Gun Wickart Johansson (Stockholm), Måns Agrup (Linköping), Hedda Haugen (Göteborg), Karin Belfrage (Lund), Jack Lindh (Umeå) For the Swedish Pediatric Radiotherapy Group (SvBRG)



P–09

Extramedullary Leukaemia in Children With Acute Myeloid Leukaemia

Heidi Kristine Støve, Aarhus University Hospital, Skejby, Department of Paediatrics, Denmark

Background Extramedullary leukaemia (EML) is a common find-ing in paediatric acute myeloid leukaemia (AML). The prognostic significance of EML is not clarified and consequently, the optimal treatment of AML patients with EML is unknown. The aim of this study was to characterize the clinical and prognostic aspects of EML. Methods The cohort consisted of children diagnosed with AML and treated according to the NOPHO-AML 2004 protocol from January 2004 to September 2013 in the Nordic countries and Hong Kong. Patients were classified by the presence of EML (CNS disease, myeloid sarcoma, or non-EML). Data on characteristics were collected from the NOPHO-AML database. Survival estimates were calculated using the Kaplan-Meier method. The prognostic factors will be examined in a multivariate analysis. Results By December 2013, 322 children treated on the NOPHO-AML 2004 protocol were registered in the NOPHO-AML database. Due to missing data, nine children were excluded from the preliminary analysis. At diagnosis, 72 (22.4%) children had EML (CNS disease and/or myeloid sarcoma). EML was associated with young age (median: 2.0 years; p = .009), FAB

M5 (p < .001), and 11q23 aberrations (p = .053). The 5-year estimated event-free survival was 55% for EML patients and 44% for non-EML patients (p = .48). The 5-year estimated overall survival was 63% for EML patients and 72% for non-EML patients (p = .032). Death during induction occurred in 8.3% of EML patients versus 0.8% of non-EML patients (p = .002). The cumulative incidence of relapse 5 years after diagnosis was 34% for EML patients versus 49% for non-EML patients; however, this was not statistically significant (p = .166). Conclusion EML was associated with young age, FAB M5, MLL aberrations, and infe-rior survival. EML is a risk factor for induction death.

Keywords Extramedullary leukaemia; AML; paediatrics

Authors Heidi Kristine Støve, Julie Damgaard Sandahl, Jonas Abrahamsson, Shau-Yin Ha, Jesper Heldrup, Kirsi Jahnukainen, Ólafur G. Jónsson, Birgitte Lausen, Josefine Palle, Bernward Zeller, Erik Forestier, and Henrik Hasle

P–10

Clinical characteristics and outcome in children with hereditary spherocytosis: A single center observational study in 35 consecutive

Tina Lund Leunbach, Aalborg University Hospital, Børneafdelingen, Denmark

Introduction: Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia in Scandinavia. Hemolysis occurs in different grades, and can be cured by splenectomy. Splenectomy is associated with a risk of sepsis, and may increase the risks of long-term thromboembolic events. Aim: to examine the clini-cal characteristics, and splenectomy rate in children with HS. Methods: We reviewed the clinical history of 35 children at the Pediatric Department Aalborg University Hospital from 1995-2012. We recorded clinical events (neonatal jaundice, transfusion depend-ent anemia, splenomegaly, symptomatic cholelithiasis, aplastic crisis, and splenectomy) and classified patients according to grade of hemolysis depending on blood samples (hemoglobin, reticulocytes, and bilirubin). The risk of splenectomy was calculated using the Kaplan-Meier method. Results: In 32 cases hemolysis was graded. 47% had mild (n=17), 34% moderate (n=12), and 9% severe (n=3) hemolysis. In the severe group all had neonatal icterus and needed erythro-cyte transfusion before 1 year of age. In the severe group 100% were splenectomized at a median age of 5.1 years, in the moderate group 58% at a median

age of 13.4 years, and in the mild group 12% at a median age of 15.4 years. At 17.5 years 40% were splenectomized. The probability of splenic survival at 6 years was 90 % (95%CI 71-96%), and at 18 years 23 % (95%CI 4-52%). Discussion: The occurrence of splenectomy increases during childhood and into adulthood. Splenectomy occurred more frequent and at an earlier age concomitantly with hemolytic activity. The probability of having the spleen at 18 years was 23 % consistent with the increased proportion of sple-nectomized parents in childbearing age. Conclusion: The occurrence of splenectomy increases with age and is reaching high levels in adult life. Prospective studies are needed among patients with HS to illuminate the risk of long-term thromboembolic events.

Keywords Hereditary spherocytosis, hemolysis, clinical events, splenectomy, thromboembolic events

Authors Tina Lund Leunbach (presenting author) Ruta Tuckuviene



P–11

Immunosuppressed children and respiratory viral infections – A prospective follow-up study

Martina Söderman, Karolinska institutet, Institution of medicine, Solna, Sweden

Introduction: Neutropenic fever is a common complication in chil-dren undergoing treatment for cancer. The etiology is only known in 15-30% of the neutropenic febrile episodes. Previous studies detected a respiratory virus in about half of the neutropenic febrile cases, but these have not been able to correlate the respiratory virus to the febrile episode. Aims: The aim of the study was to examine whether findings of a respiratory virus could be correlated to neutropenic febrile episodes by fol-lowing the patients longitudinally. We also aimed to investigate whether the shedding-time of respiratory viruses is prolonged in immunosuppressed children. Material and Methods: The study was conducted at Astrid Lindgren Children’s Hospital and children between 0-18 years that were treated for a malignancy were included. A nasopharyngeal aspirate was taken in children with neutropenic fever and sent to the micro-biology unit for PCR detection of 16 different subtypes of respiratory viruses. Re-sampling of virus-positive patients was repeated after 4-6 weeks, using the same

methods. Results: Fiftynine episodes of neutropenic fever have been collected, and in 24 episodes (41%) a respiratory virus was detected. Follow-up samples have been collected in 18 of the episodes and 13 patients had been able to clear their respiratory virus. The viruses found in the patients that had not cleared their respiratory virus were rhinovirus and coronavirus, however some of these patients had a new episode of neutropenic fever. Conclusions: The results indicate that the finding of a respiratory virus can be correlated to a neutropenic febrile episode, especially among certain type of viruses and that prolonged viral shed-ding is not a major problem in this group of patients.

Keywords Keywords: Neutropenic fever, respiratory virus, chil-dren, cancer, polymerase chain reaction

Authors Authors: Martina Söderman, Thomas Tolfvenstam, Kristina Broliden, Anna Lindblom

P–12

Diffuse Intrinsic Pontine Glioma – A Case Report of Four Children

Kirsten Brunsvig Jarvis, John Asle Bjørlykke, Maria Gunnes, Dorota Wojcik, Haukeland Universitetssykehus, Barneklinikken, Norway

BackgroundThe treatment and outcome for pediatric malignancies has improved greatly in the last few decades, but for diffuse brainstem tumors the prognosis is still dismal. We report our experience at the University Hospital of Bergen, Norway, with four patients diagnosed with diffuse pontine glioma in the period from April 2009 to September 2011 and treated according to the Angiocomb protocoll. All four patients were girls, ages five (patient A), four (patient B), nine (patient C), and six (patient D) years at diagnosis. Their symptoms at diagnosis varied from abducens nerve palsy (patients A and C), to ataxia (patient D), to acute hydrocephalus (patient B). Diagnosis was based in MRI findings, all cases were inoperable and no biopsies were performed. All four patients were treated with initial radiotherapy, 1,8 Gy x 30 fractions, totally 54 Gy, with adjuvant Topotecan as a radiosensitizer. Only one patient (patient D) had progression of the tumor during radiotherapy. Four weeks after completed radiotherapy, they started on investigational chemotherapy in the form of Thalidomide, Celecoxib, and Etoposide accord-

ing to the Angiocomb protocol. The duration of the triple therapy ranged from three to nine months, and in each case the treatment was stopped due to tumor progression; radiological, clinical, or both. The major side effect of the treatment was neutropenia. Patients B and D died shortly after the end of triple therapy; the former after three months of triple therapy, the latter after eight months and followed by alternative medicine from Tibet the last weeks of life. Patients A and C received six and seven months of triple therapy respectively, followed by alternative chemotherapy with Topotecan/Dicloracetate for six and two months respectively. Patient A also received Nimotuzomab/Vinorelbine for two months. All four patients died within two years of diagnosis.

Keywords Brainstem tumor, pontine glioma, Angiocomb

Authors Kirsten Brunsvig Jarvis, John Asle Bjørlykke, Maria Gunnes, Dorota Wojcik



P–13

Interleukin-7 levels in plasma predict the rate of T cell immune reconstitution in allogeneic stem cell transplantation

Klaus G Müller, Copenhagen University Hospital Rigshospitalet, Department of Pediatrics and Adolescent Medicine, Denmark

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by delayed T cell reconstitu-tion and acute graft-versus-host disease (aGVHD), both contributing to treatment-related mortality. Interleukin-7 (IL-7) is a cytokine essential for T-cell generation in thymus and peripheral homeostasis of T cells. We prospectively investigated associations between IL-7 levels and lymphocyte reconstitution, aGVHD and mortality in HSCT. Materials and methods: 81 paediatric and adult patients transplanted with sibling or unrelated donors at Rigshospitalet, Denmark, from 2010-2013 were included. Plasma IL-7 was measured by ELISA (R&D Systems) before transplantation, at the day of transplantation and at day +7, +14, +21, +28, +60 and +90 post-transplant. T, B and NK cells were counted using flow cytometry. Results: Plasma IL-7 rose from 2.4 gl/ml following conditioning to a peak of 22.1 pg/ml at day +7 (P<0.0001) and then gradually declined to pre-transplant levels. High IL-7 levels at day +7 were associated with the use of anti-thymocyte globulin (P=0.0079), but not with C-reactive protein levels. IL-7 level day +7 was significantly negatively associated with T cell subset counts day +30 to +60 in multivariate analysis. IL-7 levels above median (18.2 pg/ml) at day +14 tended to be associated with

acute GVHD grade 2-4 (OR=4.2, P=0.071). This was confirmed in adults when stratifying for age (OR=5.4, P=0.036). Overall survival was significantly increased in adults with low IL-7 levels at day +7 (P=0.046). Discussion: This study confirms previous findings of elevated IL-7 levels during lymphopenia, most pro-nounced in patients treated with ATG. Importantly, the present data indicate that IL-7 is determined by feed-back regulation based on the size of the total T cell population. Furthermore, high plasma IL-7 levels in the early post-transplant period can predict inferior T-cell reconstitution, possibly reflecting lower total T cell numbers early after HSCT or aGVHD mediated suppression of haematopoiesis.

Keywords Interleukin-7, allogeneic stem cell transplantation, immune reconstitution, graft-versus-host disease

Authors Katrine Kielsen, Karina Jordan, Hilde H. Uhlving, Peter L. Pontoppidan, Zaiba Shamim, Marianne Ifversen, Carsten Heilmann, Claus H. Nielsen, Henrik Sengeløv, Lars P. Ryder, Klaus G. Müller

P–14

Exosomes from MYCN-amplified neuroblastoma cells contain oncogenic microRNAs

Trond Flægstad, Univ of Tromsø and Univ Hosp North Norway, Pediaytrics, Norway

BackgroundThe MYCN oncogene is frequently amplified in neu-roblastoma and is associated with aggressive disease and treatment failure. MYCN induces expression of different miRNAs, which are posttranscriptional regulators of gene expression with established roles in neuroblastoma development. In this study, we show that MYCN -amplified cell lines not only express miRNAs with functions inside the cell, but also secrete popula-tions of miRNAs inside small vesicular structures called exosomes, with the ability to shuttle to other cells. We have isolated and characterized exosomes from MYCN amplified cell lines, and here demonstrate their ability to be taken up by other cells. By profiling the miRNA expression, we demonstrate high expression of a group of established oncomirs in exosomes from two MYCN- amplified cell lines. Despite the fact that other studies have demonstrated the ability of exosomal miRNAs to regulate their targets in recipient cells, we did not

observe this with exosomes from MYCN -amplified cells. However, exosomes were able to induce in vitro angiogenic tube formation, suggesting that they can have tumorigenic properties. These new findings reveal a potential new way for MYCN -amplified neuroblas-toma cells to interact with their environment.

Keywords Neuroblastoma, MYCN, mcroRNA, exosomes

Authors Bjørn Helge Haug1 , Øyvind H. Hald2 , Peter Utnes1, Cecilie Løkke2 , Trond Flægstad1,2 , Christer Einvik1* 1 Dpt. Of pediatrics, University-hospital of Northern-Norway (UNN) 2 Pediatric research group, Department of clinical medicine, University of Tromsø



P–15

Trisomy 8 in pediatric acute myeloid leukemia; a NOPHO-AML study

Anne Cathrine Lund Laursen, Aarhus University Hospital, Skejby, Denmark, Pediatric Oncology, Denmark

BackgroundTrisomy 8 is one of the most common cytogenetic aber-rations in acute myeloid leukemia (AML), however, the isolated effects of trisomy 8 in pediatric AML are largely unknown. Our purpose was to determine the clinical and cytogenetic consequences of trisomy 8 in pediatric AML and investigate the individual prognostic impact of this aberration. We retrospectively investigated 609 patients from the NOPHO-AML database. Complete cytogenetic data were available in 596 patients (98%), aged 0-18 years, and diagnosed from 1993 to 2012 and treated according to the NOPHO-AML 1993 and 2004 protocols in the Nordic countries and Hong Kong. We identified 87 patients (15%) with trisomy 8, in 69 patients (12%) trisomy 8 was combined with other aberrations (+8 other) and in 18 (3%) it was the sole cytogenetic abnormality. Trisomy 8 was associated with FAB M5 (36%) but otherwise clinically comparable with the non trisomy 8 group. The most common additional aberrations in the +8 other group were the MLL rearrangements t(9;11)(p22;q23) (28%) and 11q23 other than t(9;11) (15%), +19 (25%), +6 (23%), +21 (20%), +22 (13%), inv(16) (10%), and t(8;21) (9%). Pediatric AML with isolated trisomy

8 was associated with older age at onset (median age 10.2 years), 33% had FAB M2 and FLT3-ITD mutations were present in 58%. The 5-year EFS for patients with isolated trisomy 8 was 50% and 5-year OS was 75%. In conclusion, trisomy 8 was present in 15% of the cohort and was one of the most common cytogenetic aberrations in pediatric AML. Trisomy 8 is a heterogeneous group and the majority of patients have additional aberrations. Patients with isolated trisomy 8 differed from patients with +8 other and were associated with older age at onset (median age 10.2 years), FAB M2 (33%), and FLT3-ITD aberra-tions (58%). There were no differences in survival.

Keywords acute myeloid leukemia, trisomy 8, cytogenetics, pediatric, NOPHO study

Authors Anne Cathrine Lund Laursen, Julie Damgaard Sandahl, Eigil Kjeldsen, Jonas Abrahamsson, Shau-Yin Ha, Jesper Heldrup, Kirsi Jahnukainen, Ólafur G. Jónsson, Birgitte Lausen, Josefine Palle, Bernward Zeller, Erik Forestier, and Henrik Hasle

P–16

Thromboembolism in children with acute lymphoblastic leukemia in the Nordic countries

Nadine Gretenkort Andersson, Skåne Univiersity Hospital, Paediatric Haematology and Oncology, Sweden

BackgroundChildren with acute lymphoblastic leukemia (ALL) are at high risk for thromboembolism (TE) due to several factors like central venous catheters, immobi-lization, infections and treatment with asparaginase and steroids, leading to increased morbidity and mortality. Identifying the clinical risk factors and high risk treatment phases for TE is important and can lead to a better outcome and quality of life for these children. The Nordic countries have a common treatment protocol and registry for childhood ALL offering an excellent opportunity to study a large cohort of children. We conducted this prospective study on symptomatic thromboembolism in children with ALL to characterize the prevalence, the clinical characteristics, and potential clinical predictive fac-tors for symptomatic TE in children with ALL and the impact of thrombosis on treatment delays. From 2008 to 2013 the study group could include 1038 children (aged 1- 18 y) diagnosed with ALL from seven countries. The overall prevalence of thrombosis was 6.1 % (n = 64). All cases were venous TE and no arterial TE was found. Of all thrombotic events 47 % (n=30) were catheter-related, and 31 % (n=20) were cerebral venous sinus thrombosis. In univariate analyses age, mediastinal mass, stratification to high

risk protocol, T-ALL/bilineage ALL, and induction with dexamethasone were significant risk factors for TE. Of those, only age ¡Ý 15 year remained a significant risk factor in multivariate analysis. Contrary to previous international findings, most thrombotic events occurred after the induction phase. The observed mortality directly or indirectly related to thrombosis was 12% (n=7). Prophylactic anticoagulation in children with ALL and high risk for TE could lead to a lower TE prevalence with lower morbidity and mortality. It should be discussed whether low-molecular heparines or other prophylactic strategies for risk groups e.g. teenagers should be implemented in prothrombotic phases of the new NOPHO-ALL protocol.

Keywords thrombosis, acute lymphoblastic leukemia, children, asparaginase, steroids

Authors Nadine Gretenkort Andersson, on behalf of the NOPHO Thrombosis Working Group (Ruta Tuckuviene, Susanna Ranta, Jon Helgestad, Ellen Ruud, Anne Mäkipernaa, Tony Frisk, Olafur Gisli Jonsson, Kaie Pruunsild, Sonate Saulyte Trakymiene, Ulf Tedgård)



P–17

Medullary Thyroid Carcinoma in children with MEN 2B in Norway. Clinical course of an orphan disease.

Else Marie Opsahl, Oslo University Hospital, The Norwegian Radium Hospital, Department of Surgery, Norway

Background Multiple Endocrine Neoplasia Type 2B (MEN2B) is an orphan disease with an incidence below 1:500,000. MEN 2B is a combination of early onset medullary thyroid carcinoma (MTC) before 1 year of age, bilat-eral pheochromocytoma and clinical abnormalities as orofacial and conjunctival neuromas, thickened corneal nerves, marfanoid habitus and constipation (Pseudo-Hirschsprung disease) due to intestinal ganglioneuro-matosis. Early recognition and management of MEN 2B is crucial but may be challenging in Norway with 5 million inhabitants and 60,000 live births annu-ally. Material: All Norwegian patients with germ line mutations in the RET proto oncogene (n=69) were screened for MEN 2B causing mutations. Clinical and outcome data for all identified patients were collected. Results: Five patients with MEN 2B were identified giving an incidence of 1:520,000 live births and not more than 1-2 new cases per decade in Norway. The diagnosis was based on clinical recognition, confirmed by RET analysis, all with M918T de novo mutation. Median age at diagnosis was 13 (range 8-34) years. All patients had node positive medullary thyroid carcinoma and none could be biochemically cured. Median time interval between first recognition of “classical” clinical MEN 2B symptoms and syndrome diagnosis was 9 (range 4-22) years. However, neuroma and marfanoid habitus were not present before 4 to 6 years of age. Whereas the most recently diagnosed patient was

identified due to neuroma, the other patients were diagnosis based on endocrine syndrome components. After median follow up of 132 (range 13-301) months, all patients were alive. Conclusion: Even in countries with high developmental indices, management of orphan diseases such as MEN 2B remains a challenge concerning recognition and management at an early age. Recognition of the “classic” MEN 2B phenotype is not sufficient for timely detection and treatment of MEN 2B patients with de novo M918T mutations.

Keywords Key Words: Multiple endocrine neoplasia. M918T RET proto oncogene mutation. Medullary thyroid carcinoma. Intestinal ganglioneuromatosis. Orphan disease.

Authors Else Marie Opsahl1, Ann Elisabeth Åsberg2, Trine Bjøro1,3, Lovise Olaug Mæhle1, Lars Fredrik Engebretsen4, Krystina K Grøholt1, Lars Andreas Akslen4, Lars Hilmar Jørgensen1, Jan Erik Varhaug4,5 and Michael Brauckhoff 4,5 Presenting author: Else Marie Opsahl 1Oslo University Hospital, Oslo, 2St. Olavs University Hospital, Trondheim, 3Institute of Clinical Medicine, University of Oslo 4Haukeland University Hospital, Bergen, 5Department of Clinical Science, University of Bergen

P–18

Role of minor ALL-subclones carrying IKZF1 deletions in the development of relapse.

Peter Hoogerbrugge, RadboudUMC, Pediatric Oncology, The Netherlands

BackgroundRelapse is the major cause of treatment failure in childhood ALL, and improvement of risk stratifica-tion is essential for obtaining better cure rates. We and others demonstrated that the presence at diagnosis of deletions in IKZF1, the gene encoding the lymphoid transcription factor IKAROS, is a strong risk factor for relapse. Furthermore, preliminary results show that these deletions can be present at subclonal levels, often undetectable by routine methodologies. These findings are in line with recent studies, which have shown a complex, dynamic architecture of clonal diversity in ALL, both at diagnosis and at relapse. This multiclonal diversity likely contributes to the selective outgrowth of therapy-resistant leukemic cells during or after chemotherapy treatment, resulting in relapse. Whether subclonal deletions in IKZF1 are also associated with relapse has not been thoroughly investigated. Several recurrent intragenic deletions in IKZF1 show clustering of their genomic breakpoints, which allows efficient detection of subclonal deletions by breakpoint-spanning PCR. Using this method, we screened a cohort of 331 B-cell precursor ALL patients, treated according to the DCOG-ALL9 and ALL10 protocols, for the presence of subclonal exon 4-7 IKZF1 deletions (IKZF1Δ4-7) at diagnosis. The cohort was

slightly enriched for relapsed cases (36.6%). A total of 34 IKZF1Δ4-7 deletions were found, of which 17 were not detected by routine MLPA. All deletions carried unique breakpoints and TdT-mediated non-templated sequences. The 17 MLPA-negative cases had an allelic burden of the IKZF1Δ4-7 deletion varying from 28% to <1%. Whereas 12 cases with full clonal IKZF1Δ4-7 deletions eventually relapsed, only 6 cases with sub-clonal IKZF1Δ4-7 deletions developed a relapse. In none of the cases for which material was available for testing (n=4), subclonal lesions were detected in the relapsed clone. Our data suggest that, in contrast to clonal IKZF1Δ4-7 deletions, subclonal deletions of IKZF1Δ4-7 rarely contribute to relapse in ALL.

Keywords ALL, IKZF, genomics

Authors Peter Hoogerbrugge, Esme Waanders, Anke den Engelsman, Simon van Reijmersdal, Jiangjan Yu, Edwin Sonneveld, Rob Pieters, Ad GeurtsvanKessel, Frank van Leeuwen, Roland Kuiper; Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; DCOG, The Hague, Netherlands



P–19

6-Thioguanine and 6-Mercaptopurine Combination Maintenance Therapy of a Girl with pre-B ALL

Stine Nygaard Nielsen, Rigshospitalet, BørneUngeKlinikken, Denmark

Background Maintenance therapy (MT) with oral methotrexate (MTX) and 6-mercaptopurine (6MP) has proven essential to eliminate residual disease and attain cure in childhood acute lymphoblastic lymphoma (ALL). Still, contemporary MT is challenged by treatment related hepatotoxicity, indirect parameters for monitoring treatment efficacy and currently lacking intensification regimens. The interindividual variability in response to 6MP is strongly associated with the genetically determined activity of the 6MP metabolizing enzyme TPMT. The vast majority of patients (90%) has high TPMT activity (homozygous for functional TPMT alleles). Yet, patients with low TPMT activity (carry-ing a non-functional TPMT allele) have higher levels of thioguanine nucleotides (TGNs), lower levels of hepatotoxic methylated 6MP metabolites (MeMPs) and lower relapse rates. Addition of 6-thioguanine (6TG) to MT of patients with high TPMT activity will mimic the more favorable thiopurine metabolite profile seen in patients with low TPMT activity, as 6TG is a poor substrate for TPMT and 6TG is more directly metabolized to TGNs. Case Report: An 8 year-old girl with pre-B ALL and high TPMT activ-ity was treated with MTX/6MP/6TG therapy during the maintenance phase. After 52 days with 6TG

therapy (6TG max. dose of 10 mg/m2/day) the thio-purine metabolite profile (Ery-TGN/Ery-MeMP) had increased 5.5-fold due to both a lowered MeMP-level and an increased TGN-level. No hepatotoxicity was observed during 6TG therapy. Discussion/Conclusion: MTX/6MP/6TG MT proved feasible and altered the thiopurine metabolite profile in a patient with high TPMT activity. Alternative approaches of lowering the level of MeMPs have been proposed. Both split-dose administration of 6MP and allopurinol-mediated inhibition of 6MP-methylation have been successful in reducing MeMP-levels and hepatotoxicity. However, none of these approaches seem sufficient in address-ing the lack of intensification regimens. A prospective clinical phase 1-2 trial testing MTX/6MP/6TG MT in patients with non-B cell NHL and high TPMT activity is to be conducted.

Keywords Maintenance therapy, ALL, TPMT, 6-thioguanine.

Authors Stine Nygaard Nielsen, Thomas Leth Frandsen, Jacob Nersting, Lisa Hjalgrim, Kjeld Schmiegelow BørneUngeKlinikken, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.

P–20

Early human germ cell development.

Jan-Bernd Stukenborg, Karolinska Institutet, Department of Women’s and CHildren’s Health, Sweden

Objectives: When primordial germ cells (PGCs) colonize the developing gonads at the genital ridge they start expressing genes such as KIT, PLAP, MAGE-4A, and DDX4. This expression panel is also displayed by germ cell tumors and thereby supports the hypothesis that GCTs originate from the precursor carcinoma in situ, that are differentially arrested PGC/gonocytes. The differentiation of PGC/gonocytes in humans is not synchronous and thereby leads to the simultaneous presence of different subtypes of gonocytes during fetal development. Methods: Gonadal tissue pieces of 5.5 to 10.5 weeks old human fetuses were cultured as organ cultures up to 3 weeks with or without hCG and rFSH stimulation. Samples for immunohisto-chemical evaluation were fixed in 4% paraformal-dehyde overnight at 4ºC and embedded in paraffin. Tissue samples for transmission electron microscopy were fixed in glutaraldehyde and embedded in Epon. Immunohistochemistry and immunofluorescence were used to detect and characterize protein expression in different cells/tissue compartments and follow the temporal distribution of various proteins e.g. KIT, POU5F1, DDX4 and VIMENTIN. TUNEL assay was used to define the overall survival rate before and after culture periods. Results: The amount of apoptotic cells after 14 days of culture was between 0.11 and 1.23%. The expression of KIT, POU5F1, DDX4 and

VIMENTIN was observed after 14 days in vitro. In vitro testicular cord formation of 6.5 weeks old male fetal gonads cultured for 21 days exhibited similar cord formation morphology observed in 9.5 weeks old control tissue. Conclusions: Our study demonstrates that organ culture of human fetal gonadal tissue gives rise to viable tissue expressing proteins present in germ and somatic cells and a similar testicular cord formation found in age-matched control tissue. Therefore, the study provides an ideal platform for ongoing experi-ments to investigate specific cellular mechanisms in early human gonadal development and its failures.

Keywords testis, germ cell tumors, in vitro spermatogenesis, fertility, germ cells

Authors Kristín Rós Kjartansdóttír1*, Rika Lindh1*, Ahmed Reda1, Valentina Pampanini1,2, Outi Hovatta3, Olle Söder1, Jan-Bernd Stukenborg 1 1Department of Women’s and Children’s Health, Pediatric Endocrinology Unit; Q2:08; Karolinska Institutet and University Hospital, SE-17176 Stockholm, Sweden; 2Bambino Gesu` Children´s Hospital, Piazza di Sant’Onofrio, 4, 00165 Roma, Italia, 3CLINTEC, Division of Obstetrics and Gynecology, Karolinska Institutet, Huddinge, Sweden



P–21

Organ culture of rodent testicular tissue – Optimization of fertility preservation strategies.

Jan-Bernd Stukenborg, Karolinska Institutet, Department of Women’s and Children’s Health, Sweden

Objectives: Late side effects affecting future fertility in children undergoing gonadotoxic treatments do still exist. So far, no treatment can be offered to rescue fertility in those patients. In 2011, Japanese researchers demon-strated for the first time viable offspring from in vitro generated murine sperm using an organ culture. This experiment is big step towards the establishment of clinical tools to use in vitro differentiated gametes as potential fertility preservation for young cancer patients. More studies are required to meet efficiency/safety concerns and translate results to the situation in humans. To address this, we established the testis organ culture in our group and started to adapt the conditions described for mouse to rat. Methods: Organ cultures of pre-pubertal 5dpp rat and 3dpp mouse testes were setup by cutting the testes into pieces. The tissue frag-ments were positioned with or without adipose tissue pieces on the agarose gel strands placed in 6 well culture plates and cultured in MEMα medium±Glutamax at 35°C in 5% CO2 for up to 52 days. Cell proliferation and expression of proteins specific for testicular cells were evaluated after up to 52 days in rats and up to 35 days in mouse organ cultures. Results: A positive

effect of adipose tissue on peritubular cell function was found. Morphological evaluation revealed a similar spermatogenic development in vitro when compared to the situation in vivo. Proliferation of germ cells could be observed up to 35 days in murine and 52 days in rat tissue. Conclusions: Our study demonstrates, an activation of peritubular cells and the expression of proliferation markers in cultured murine and rat tissue for 35 and 52 day, respectively. Therefore, we conclude that the organ culture, established for murine testicular tissue, can be applied to other species, for male germ cell differentiation in vitro.

Keywords testis, late effects, in vitro spermatogenesis, fertility, germ cells

Authors Ahmed Reda, Mi Hou, Halima Al-Balushi, Rika Lindh, Olle Söder, Jan-Bernd Stukenborg Department of Women’s and Children’s Health, Pediatric Endocrinology Unit; Q2:08; Karolinska Institutet and University Hospital, SE-17176 Stockholm, Sweden

P–22

Effect of basic culture media. – Do the storage and media per se affect testicular tissue?

Jan-Bernd Stukenborg, Karolinska Institutet, Department of Women’s and Children’s Health, Sweden

Objectives: Experiments focusing on the establishment of a system for in vitro differentiation of human male germ cells in the frame of the recently launched NORDFERTIL, will include those boys undergoing an oncological treatment who have a very high risk of infertility. By combination of testicular biopsies of those cases a sufficient num-ber for high quality based research can be obtained. Therefore, this study aims to evaluate the effects of different media on pre-pubertal rat testicular tissue storage for 24 hours at 6-8°C to mimic the situation given by a transport on ice within one day. Methods: Testicular tissue of pre-pubertal 5dpp rats were stored in seven different culture media for up to 24 hours at 6-8°C. Cell proliferation was evaluated by immuno-histochemistry. Testicular tissues stored for up to 24 hours in the refrigerator, were stimulated for 24 hours with 5IU/L hCG and rFSH at 35°C and 5% CO2 in order to measure testosterone production. Analysis of genes related to spermatogenesis, proliferation, apoptosis, steroidogenesis, angiogenesis and energetics was done by using TLDA assays. Results: Among the investigated 90 genes, Tk1 and Sdha gene expression was significantly higher in DMEM-Glutamine stored tissue after 12 hours. However, after 24 hours, there was no difference at all between the different media in

gene expression. In addition the storage for 12 hours at this conditions revealed in a higher production of testosterone when cell were stimulated for 24 hours with hCG and rFSH, but there was no difference between the different media used. Conclusions: In this study, we show that the media per se has no or only a minor effect on the expression of genes related to spermatogenesis, steroidogenesis, proliferation and apoptosis, angiogenesis, and energetic profiles of tes-ticular cells when stored at 6-8°C for up to 24 hours.

Keywords testis, fertility preservation, late effects, germ cells

Authors Ahmed Reda1, Karin Reuter2, Valentina Pampanini1,3, Kristin Rós Kjartansdottír1, Mi Hou1, Olle Söder1, Jan-Bernd Stukenborg1 1Department of Women’s and Children’s Health, Pediatric Endocrinology Unit; Q2:08; Karolinska Institutet and University Hospital, SE-17176 Stockholm, Sweden, 2Centre of Reproductive Medicine and Andrology, University of Muenster, 48149 Muenster, Germany, 3Bambino Gesu` Children´s Hospital, Piazza di Sant’Onofrio 4, 00165 Roma, Italia



P–23

Antibiotics Prior to Insertion of Central Venous Catheters does not prevent Bacteremia in Children with ALL

Kristin Thrana Bergmann, Aarhus University Hospital, Pediatric Department of Hematology and Oncology, Denmark

Background The efficacy of prophylactic antibiotics at the time of central venous catheter (CVC) insertion has been debated. The aim of this study was to evaluate if the administration of broad-spectrum antibiotics at the time of initial CVC placement reduces the subsequent risk of bacteremia and CVC removal due to infection. Methods All patients diagnosed with newly diagnosed ALL from January 1997 to January 2014 and treated at the Pediatric Department of Hematology and Oncology at Aarhus University Hospital, Denmark were included. Data on infectious episodes were included until removal of the nt-CVC. Results During the study period 182 patients were included. A nt-CVC was placed in 145 patients representing 3,000 CVC-days and 37 received a tunneled CVC (t-CVC) at diagnosis. Antibiotics were administrated to 69 (48%) of the patients with nt-CVC. Of the 37 patients with t-CVCs seventeen (46%) received antibiotics at time of CVC insertion. Nt-CVCs were removed after a median of 21 (range

1-56) days and 8 (5.5%) were removed due to infection. No significant difference in median CVC survival or removal due to infection was noted between patients receiving antibiotics prior to CVC insertion compared with patients not receiving antibiotics. A high rate of bacteremia was registered in patients with nt-CVC (12/1.000 CVC-days) independent of the use of anti-biotics at insertion. Conclusion Our data suggest that administration of antibiotics at time of CVC insertion does not reduce the risk of subsequent bacteremia and catheter removal in children with newly diagnosed ALL.

Keywords ALL, antibiotics, CVC, bloodstream infection, prophylaxis.

Authors Kristin Thrana Bergmann, Mette Møller Handrup, Henrik Hasle and Henrik Schrøder.

P–24

Self-perception and self-esteem consequences of CNS malignancy and brain tumour treatment in childhood/adolescence: Population-based survivor and general population outcomes compared

Krister K. Boman, Karolinska Institutet, Department of Women’s and Children’s Health, Childhood Cancer Research Unit, Sweden

BackgroundSurvivors of paediatric central nervous system (CNS) tumours are at risk for persistent tumor/treatment-related morbidity, physical disability and social con-sequences which may intrude into self-perception, vital for mental health and quality of life. Within the longitudinal Swedish CNS tumour LIFE-study, we studied the long-term impact of the childhood CNS tumour and its’ treatment on self-perception in significant domains in adult survivors, by compar-ing outcomes with those of the general population. METHODS: The target cohort included 700 Swedish survivors diagnosed between 1982 and 2001 with a primary CNS tumor. Comparison data were collected from a stratified general population random sample. Survivors and general population individuals were compared as regards self-perception in five domains: body image, sports/physical activities, peers, work, and family, and as regards a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified. RESULTS: The study group from which complete data was received included 528 survivors, 75.6% of the entire national study cohort. The control sample consisted of 995 individuals, 41% of the 2,500 addressed. Survivors had significantly poorer self-perception outcomes in

domains of peers, work, body image, sports/physical activities, and in the global self-perception index, compared with those from the general population (all P<0.001). Within the survivor group, female gender and persistent visible physical appearance sequelae pre-dicted poorer outcomes in several of studied domains. CONCLUSION: Intrusion into self-perception appears as a potential long-term psychological late effect in adult survivors after paediatric CNS tumours and the brain tumour treatment. Because of this risk, patient care and psychosocial follow-up should include psychological identity-addressing screening measures similar to what was used in this study. Paying attention to self-perception in follow-up care enables identifying, preventing, and managing of here identified adverse psychological impact of the illness on self-identity, crucially related to mental health and quality of survival.

Keywords CNS tumours, adult survivors, long-term late-effects, psychological impact, identity

Authors Lina Hörnquist, Jenny Rickardsson, Birgitta Lannering, Göran Gustafsson, Krister K Boman*



P–25

Assessment Of Transfusion Burden With Erythrocyte Concentrates In Children Treated For Acute Lymphoblastic Leukemia According To Nopho All-2008 Protocol

Jelena Rascon, Children‘s Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Center for Pediatric Oncology and Hematology, Lithuania

BackgroundThe current long-term survival rate of children treated for acute lymphoblastic leukemia (ALL) exceeds 80%. Iron overload related to the numerous transfusions of erythrocyte concentrate (EC) during intensive chemo-therapy is an emerging problem among long-term survivors. However in the clinical routine the amount of the transfused EC is rarely being traced. The aim of our study was to assess the number of EC transfu-sions during the chemotherapy according to NOPHO ALL-2008 protocol. METHODS. Retrospective analysis of patient records’ treated at our institution for ALL according to NOPHO ALL-2008 protocol was performed. Patients who completed the treatment or entered the Maintenance-2 phase of the protocol and were alive at the time of evaluation were included. RESULTS. Totally 78 patients were treated according to NOPHO ALL-2008 from 2009 till 2012. Data of 64 (82.1%) met the inclusion criteria. Risk group distribution was as follows: SR=35 (54.7%), IR=26 (40.6%) and HR=3 (4.7%). All three HR-patients received HSCT in CR1. Median age at diagnosis in

the SR vs IR vs HR was 3.6 years (75% range: 3.0-5.2) vs 8.6 years (75% range: 4.5-11.4) vs 14.6 years (75% range: 10.7-15.6) respectively. Mean volume of trans-fused EM adjusted to recipient body weight did not differ between SR vs IR groups (115.9±58.6 ml/kg vs 123.0±75.5 ml/kg, p=0.95). However it appeared to be significantly higher in HR group (300.7±326.7 ml/kg) as compared to both SR and IR groups (p=0.003 and p=0.004 respectively). CONCLUSIONS. Transfusion burden is significantly higher in children treated in the HR arm of the NOPHO ALL-2008 protocol. Transfusion history should be carefully monitored in this group of patients. After the completion treatment iron overload should be regularly checked for resolution.

Keywords Acute lymphoblastic leukemia, NOPHO ALL-2008 protocol, survivors, iron overload

Authors Rugile Cesaite Jelena Rascon

P–26

JMML with germlineCBL mutation in 1 year old girl, succesful outcome without treatment.

Anita Andrejeva, Haukeland University Hospital, Pediatric oncology, Norway

BackgroundJMML with germline CBL mutation in 1 year old girl, succesful outcome without treatment. Anita Andrejeva, Haukeland University Hospital, Norway Henrik Hasle, Aarhus University, Aarhus, Denmark 1year old girl was admitted to the hospital due to prominent splenomegaly(spleen 15 cm under costal margin). She was in good clinical condition, weight 9,83 kg, height 79 cm, no fever. Slighly delayed motor development. Stenosis of the pulmonal artery. Granulomatous rash: juvenil xantogranulomas from age 3 moths. Broad forehead, low nasale bridge. Blood tests showed anemia Hb 6,7 g/dl, WBC 89 ×10**9/l, PLT65 ×10**9/l, monocytes 24%, blasts 5%, reticulocytes 1,140 × 10**12(↑). HbF 8,2%(↑). Flowcytometry of bone marrow, bone marrow biopsy shows hypercellular bone marrow with 7% blasts , 11% monocytoid cells. She was dependent of blood and platelet transfusions. Bone marrow with monocytosis and hypercellular bone marrow. Diagnosed as JMML with homozygot mutation of CBL exon 8, germline origin. No mutation KRAS, NRAS or PTPN11. Patient was clinically stable without chemotherapy treatment. After four months patient developed SVK releated Staph. aureus sepsis requiring intensive care unit for one week. No trasfusion dependent 6 months after JMML diagnosis. 1 and ½ year after diagnosis she is still in good clinical condition, still has massiv splenomegaly, liver 3 cm under costal margine. Hb

9,7 g/dl, WBC 19,1 × 10**9/l, PLT 48 × 10**9/l, reticulocytes 0,157 × 10**12/l, HbF 6,5%. Patient`s older brother has slight motor development, multiple juvenile xantogranulomas in the skin with tendency to dissapear, broad forehead, spleen palpable 2 cm under costal margin monocytosis in blood test, normal WBC and PLT, no anemia, heterozygot CBL exon 8 mutation. Patient`s farther has heterozygot CBL exon 8mutation, no dismorphic futures, normal blood test. Grandparents has no CBL mutation. Conclusion. Germline CBL mutation predispose to juvenil myelomonocytic leuke-mia, cause developmental and functional adnormalities, cause Noonan syndrome- like phenotype. Patients with JMML and CBL mutation should be closely observed without HSCT because of high chanse for spontaneuos remission of JMML. Patients have high risk of vascular pathology developing(Retrospectiv analisys of 21 children with JMML and CBL muta-tion. Ch. Niemeyer, M. W. Kang, D. Shin, H.Hasle et al, NatGen sep.2010).

Keywords JMML, CBL mutation

Authors Anita Andrejeva, Haukeland University Hospital, Bergen, Norway Henrik Hasle, Aarhus University, Aarhus, Denmark



P–27

Intercranial Hemorrhage in Children with Immune ThrombocytoPenia (ITP)

Mimi Kjærsgaard, Aarhus University Hospital, on behalf of the Platelet Working Group

The risk of intercranial hemorrhage (ICH) is still an issue in ITP. Earlier published frequency is 0.1-0.6%. We report six cases of ICH in the Nordic countries from 1998 to 2014.At diagnosis the children were median 10.5 years old, and the platelet count was <5x109/L. Within 48 hours after ITP diagnosis two children received intravenous immunoglobulin (IVIG), one steroids, two have unknown treatment status, and one was untreated.Four children were generally unwell with increasing bleeding symptoms the days before ICH. Three chil-dren decreased 17g/L, 63g/L, and 50g/L in hemoglobin, 10 hours, two, and 14 days before ICH, respectively. One case reported a head trauma. Case 2 had a coup-contrecoup injury on CT scan, but trauma was not confirmed. Three of the six children received IVIG three, two, and seven days before ICH. Case 6 was treated during her disease course with steroids (prednisolone, beta-methasone, methylprednisolone), IVIG, azathioprine, and Nplate with no significant response to any of the medications. Case 2 received IVIG only at diagnosis of ITP, 20 days before ICH.

The true ICH frequency in ITP has not yet been documented. Likely, the only ITP related ICH cases not captured here, are children dying from ICH with undiagnosed ITP. Hence, the six cases represent at least 75% of all the ICH cases in the five Nordic countries during the 16 years period. There are 4.7 million children in the Nordic countries, and the incidence of newly diagnosed ITP is 4.8/100,000. With these assumptions, the yearly incidence of ICH in ITP is 0.22%. Initial ITP care has moved towards a watch-and-wait approach, and the important question is, whether more children are put at risk for ICH. At least five of the six children received one or more medical treatments before ICH occurred. However, unexplained Hgb-decrease should raise suspicion of occult bleeding.

Keywords ITP, ICH, bleeding symptoms, hemoglobin decrease

Authors Mimi Kjærsgaard

Photo: Bergen Tourist Board / Oddleiv Apneseth

NOPHO Poster Presentation


NOBOS PROGRAMME

Sat u r day 10 May 19:00–21:00 Ice breaker – Radisson Blu Royal, Bryggen

Sunday 11 May

8:30 Opening ceremonyChair: Britt Ingunn Sævig

09:00–10:30 Joint session with NOPHOHow does cancer treatment affect the developing child, and what can we do to help children integrate the hardship they experienceMarianne Straume, Cand. Psychol. Psychologist, Specialist in clinical psychology, Bergen


11:00–11:45 Ethical dilemmas when treating seriously ill childrenTrond Markestad, professor of Pediatrics, University of Bergen, Research coordinator at the Department of Pediatrics, Haukeland University Hospital, Bergen, Research advisor at Hospital Innlandet Trust, Eastern Norway

11:45–12:30 3x15 min oral presentations from Ethics group – NOPHO/NOBOS

A Nordic platform for clinical ethics in pediatric oncologyPernille Wendtland Edslev, Aarhus

Treatment decisions in pediatric health care- Who’s the one to decideLisa Törnudd, Linköping

Conceptual clarity of values in end-of-life deliberations in pediatric oncologyAnders Castor, Lund

12:30–13:30 Lunch

13:30–13:45 Opening NOBOSChairs: Sigrún Þóroddsdóttir and Sunni Helland

13:45–14:30 Keynote lectureWhy, when, where and how to inform parents within paediatric oncology?Anders Ringnér, PhD, Senior lecturer, Umeå University

14:30–15:00 Break

15:00–15:45 Free papers 15:00–15:20 Infringing on autonomy – an ethical concern experienced by nursing staff.

Cecilia Bartholdson, Sweden

15:25–15:45 Children and adolescents’ experience of donating bone marrow / stem cells to surviving siblings. Carina Rinaldo, Katarina Wallin, Sweden

18:00 NOBOS dinner at USF Verftet

92 93 N O P H O / N O B O S A N N U A L M E E T I N G – B E R G E N 2 0 1 4 N O P H O / N O B O S A N N U A L M E E T I N G – B E R G E N 2 0 1 4

Mo nday 12 May 201406:30–07:30 Fun and Run. Meeting point Radisson Blu Royal

09:00 OpeningChairs: Anders Rignér and Kjerstin Mongstad

09:15–10:00 Keynote lectureYouth and rehabilitationMay Aasebø Hauken, PhD student Hemil, UIB / Røde Kors Haugland Rehabilitation Centre, Center for Crisis Psychology, Bergen

10:00–10:45 Poster presentations

10:45–12:30 Free papers10:45–11:05 Appetite, senses and joy of life- a nutrition project.

Anne Kaspersen, Denmark

11:05–11:25 The process of striving for an ordinary, everyday life, in preschool aged children living with cancer, during the first year post diagnosis.Laura Darcy, Sweden

11:30–11:45 Break

11:45–12:05 Homecare nursing. Houtari Eila, Finland

12:05–12:25 Local anesthetic of intramuscular Asparginase. Margaretha af Sandberg, Sweden

12:30–13:30 Lunch

13:30–14:15 Chairs: Mariann Hvarnes and Marianne Bøe

Keynote lecturePsychosocial health and quality of life and social support in children and adolescents who survive cancerMary-Elizabeth Bradley Eilertsen, Dr. Philos, Centre for Health Promotion Research HisT / NTNU, Trondheim.

14:30–15:30 Working groups / NOBOS Board meeting

Nutrition ................ Maria Molin and Carina FondinPain ......................... Margaretha af SandebergPalliative care ......... Marianne S.BentsenLate effects .............. Elna HamiltonRehabilitation ......... Mary E.Bradley Eilertsen


16:00–17:00 National meetings

19:30 Festive dinner at Grieghallen

tu e S day 13 May

09:00–09:15 News from NOBOSChairs: Marianne Bentsen and Eila Huotari

09:15–10:00 Keynote lectureTo loose a child to cancerUlrika Kreicbergs, Registered Nurse and Researcher at the Department of Women’s and Children’s Health, Karolinska Institute, Stockholm.

10:30–12:15 Free papers10:30–10:50 Visiting nursing experiences working bedside in the only pediatric

oncology ward in Ethiopia. Hilde Frøland Hauge, May Morken, Norway

10:55–11:15 Study of childrens’ experiences with venous acces (vap). Need for a Nordic study? Steinunn E Egeland, Norway

11:15–11:30 Break

11:30–11:50 Complications related to gastrostomy in children and adolescents with cancer.Tina Ekängen, Johanna Kjellberg, Sweden

11:55–12:15 Kit for symptomatic relief for children in the terminal stage. Marianne Bentsen, Norway

12:15–12:20 Presentation of next NOBOS conference 2016 in Iceland

12:20–12:30 Closing remarksGitte Petersen, NOBOS Board

12:30 Lunch to go


KEYNOTE SPEAKERS

Mary-Elizabeth Bradley EilertsenLecturer/Senior Lecturer, Dr. Philos, Centre for Health Promotion Research HisT / NTNU, Trondheim

Children and Adolescents Surviving Cancer: Psychosocial Health, Quality of Life (QoL) and Social Support

BackgroundChildhood cancer involves a crisis for the child and their family where they face many challenges to achieve nor-mality after diagnosis, even after successful treatment.

AimThis study focuses on social support, psychosocial health and QoL for children and adolescents surviving cancer. The specific aim was to explore and describe social support in view of professionals’ perception of collaboration. Moreover, this study sought to explore and describe psychosocial health and QoL of chil-dren and adolescents surviving cancer at least 3 years after their cancer diagnosis, compared with a healthy control group.

Material and MethodsHealth and non-health professionals from the families’ home communities caring for children treated in Mid-Norway, between 1990 and 1996 were invited to par-ticipate in part 1 of this study. Part 2 was a case-control

study including 50 children and adolescents diagnosed with cancer between January 1, 1993 – January 1, 2003.

Results and conclusionTo improve the child’s psychosocial health and QoL our results indicate that a collaborative approach is an important resource for social support and is essential in planning and implementing the necessary interven-tions for long-term follow-up care and rehabilitation for children and adolescents with cancer, especially for survivors with brain tumours, and those with late effects. To gain a comprehensive understanding our results also show the need to particularly take into account subjectively perceived and proxy reported QoL.

NOBOS KEYNOTE SPEAKERS


May Aasebø HaukenRN, researcher; Center for Crisis Psychology, Bergen, Norway

Rehabilitation of young adult cancer survivors

Background Cancer in young adults (18–35 years) is rare, but the vulnerable phase of life and the intense cancer treatment increase their risk of lifelong threats to health. There is limited knowledge about rehabilitation interventions for this population.

Purpose To investigate if a tailored, complex and goal-oriented rehabilitation program for young adult cancer survivors (YACS) improved participation, quality of life and physical capacity.

Method Twenty YACS with different cancer diagnoses were allocated to a six-month rehabilitation program focusing on goal setting, exercise, psychoeducation, individual follow-up and peer support.

Results The participants were unprepared for re-entering everyday life, and experienced a range of late effects, lack of understanding, and felt neither sick nor healthy. After attending the rehabilitation program, the partici-pants reported increased participation, quality of life and physical capacity. These results were explained by building capacity and finding the balance, gaining new insight and follow-up.

Conclusions A complex cancer rehabilitation programme especially tailored for YACS seems to build positive health out-comes such as participation, QOL and physical capacity in a long-term perspective. The results underline the importance of targeting rehabilitation interventions to YACS in need after cancer treatment, acknowledging rehabilitation as a process that requires adequate time and follow-up.

Anders RingnérRN, PhD, Senior lecturer, Department of Nursing, Umeå University, Umeå University Hospital, Sweden

Why, when, where and how to inform parents within paediatric oncology?

Information about the illness and its implications is a key factor for parents of children with cancer. Nevertheless, many parents experience low satisfaction with the information provided. As a starting point for this research project, we interviewed health care professionals and parents about their experiences of information. Health care professionals described dif-ficulties in matching the amount of information to the parents’ needs and shortcomings in responsibili-ties, setting, timing, and language when parents were informed. The parents felt acknowledged as persons of significance when the information worked well. However, some parents felt abandoned at important milestones and were forced to nag for information. We also studied the interaction between parents and health care professionals and identified different patterns depending on how active parents were the interaction combined with the health care professionals primary focus of the interaction.

Grounded on these findings and previous research, we designed a person-centred information intervention aiming at parents of children with cancer. So far, it has been pilot tested on eight parents. They were highly satisfied with the person-centred information inter-vention and perceived benefits from having their own time to discuss the child’s disease and pose questions that they otherwise would not have an opportunity to ask. However, no effects from the intervention were demonstrated on perceived stress, physical symptoms of stress, anxiety, and depressive mood.To sum up, central tasks are to assess the amount of and what information the parents need, to pay attention to possible differences in information needs between parents and children, and, to organise the care so that the responsibilities are clear and that parents are met in a calm setting. Improvements at important milestones during the illness period should be prioritised.

NOBOS KEYNOTE SPEAKERS NOBOS KEYNOTE SPEAKERS


Ulrika KreicbergsRegistered Nurse and Researcher at the Department of Women's and Children's Health, Karolinska Institute, Stockholm

Information about a child´s imminent death in cancer – impact on family members long-term psychological health

ObjectiveTo assess the impact of communication in pediatric oncology on bereaved family members’ long-term psychological health.

MethodsSwedish parents and siblings who lost a child, brother or sister to cancer 2-9 years earlier were invited to par-ticipate in postal questionnaire studies. 449 bereaved parents out of 561 (80%) participated, 251 mothers (56%) and 191 fathers. 174 out of 240 bereaved sib-lings (73%) participated, 73 (42%) brothers and 101 sisters. The analysis focused on the risk of psychological morbidity.

ResultsMost parents (86%) want immediate information about the incurability of their child’s malignancy. Short awareness time (<24 hrs) about their child’s imminent death commonly due to lack of relevant formation and ongoing curative treatment was found to be associated with a two fold increased risk of depression among parents and an 8-fold increase risk of sick-leave among fathers. Most siblings (55%) avoid talking to their par-ents about their deceased brother or sister in respect of their parents feelings. This entails a two-fold increased risk of anxiety.

ConclusionHealth care staff in pediatric oncology should provide information about imminent death to family members in attempts to mitigate long-term psychological mor-bidity after the loss of a child.

Photo: Bergen Tourist Board / Philippe Brechet

NOBOS KEYNOTE SPEAKERS

100 N O P H O / N O B O S A N N U A L M E E T I N G – B E R G E N 2 0 1 4

O–01 Infringing on autonomy – an ethical concern experienced by nursing staff

O–02 Children and adolescents experience of donating bone marrow / stem cells to surviving siblings

O–03 Appetite, senses and joy of life – a nutrition project.

O–04 The process of striving for an ordinary, everyday life, in preschool aged children living with cancer, during the first year post diagnos.

O–05 Home care nursing – since 2002 in Helsinki

O–06 Local anesthetic of intramuscular asparaginase

O–07 Visiting nursing experiences working bedside in the only pediatric oncology ward in Ethiopia

O–08 Study of children’s experiences with venous port access (vap). Need for a nordic study?

O–09 Complications related to gastrostomy in children and adolescents with cancer

O–10 Kit for symptomatic relief for children in the terminal stage

Overview

FREE PAPERS

ORAL PRESENTATIONS


NOPHO / NOBOS


O–01

Infringing on autonomy – an ethical concern experienced by nursing staff

Bartholdson, C., Lützén, K., Blomgren, K., Pergert, P. Women and Children’s Health, Karolinska Institutet, Children’s Cancer Research Unit Q6:05, Astrid Lindgrens´Hospital, Stockholm, Sweden

BackgroundA study regarding ethical issues and ways to deal with them has been conducted in pediatric cancer care. Ethical issues are common in pediatric care and arise in connection with value conflicts within an individual and/or between individuals, concerning which of the possible options should be chosen. Each child’s specific situation might lead to disagreements about treatment and care. Furthermore, in pediatric care, children’s growing autonomy has to be considered.

ObjectiveThe purpose of this presentation is to describe one of the ethical concerns which were identified in our study and experienced by nursing staff when caring for children with cancer.

MethodPhysicians, registered nurses and nurse aides working at a children’s hospital in Sweden answered a question-naire. Qualitative content analysis was applied to the open-ended answers.

Results/ ConclusionTo infringe on a child’s autonomy is not to give the child a chance to decide upon care related concerns by her/himself or to oppose the child’s wishes and perform actions and caring procedures that the child does not want. Nurse and nurse aide participants described children’s autonomy as something that can be violated and they experienced powerlessness in these situations. Inflicting suffering and limiting truth-telling are subcategories to infringing on autonomy.Health care professionals’ experiences of ethical con-cerns when, caring for children with cancer, seem to produce strong feelings and moral confusion among nursing staff. Not wanting to inflict suffering on the child and feeling prevented from telling the truth about the circumstances of the child’s illness are some examples of nursing care responsibilities that often are connected to medical treatment decisions.

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O–02

Children and adolescents experience of donating bone marrow / stem cells to surviving siblings

Carina Rinaldo, Katarina Vallin, Department of Pediatric Oncology and Hematology, Uppsala University Children’s Hospital, Sweden

BackgroundFamily and sibling relationships are affected in both positive and negative ways when a child in the family is afflicted with a severe illness during a long period of time. There are few national studies conducted in Sweden on how siblings who were bone marrow /stem cell donors think and feel about their experience.

ObjectiveThe aim of this study was to describe children’s and adolescents’ experiences of donating stem cells to a sick sibling in Sweden.

MethodA descriptive interview study with an inductive approach was performed using qualitative content analysis. The six participants were of both sexes and between 11-21 years. They were recruited from three different children’s transplant centers, had donated stem cells before the age of 17 and all had surviving siblings.

ResultThe theme proud heroes without a choice summarize the results. The category proud but anxious to be a donor describes a desire and a joy to help, but also concerns how they would endure the procedures and a concern of not being good enough as a donor. They were very anxious for their sick sibling. The category heroes without real choices in need of support high-lights the strong family ties make them not having a choice situation for the donation, but a need of support from their environment, healthcare and from receiving information but also all of its weaknesses. Conclusion: These donors were happy to contribute to the sibling’s recovery. They were proud and gained a positive view of life from this experience. However the questions remain who will consider the psychological risks of these children and adolescents and if it is right to expose young siblings to this risk.

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NOBOS Or al Presentation NOBOS Or al Presentation


mailto:[email protected]


O–03

Appetite, senses and joy of life – a nutrition project

Anne Kaspersen, Naja Panduro, Dorte Ellegaard Jensen, Children’s Oncology Ward, 303B Aalborg University Hospital, Denmark

The project is towards children admitted to the paedi-atrics oncology ward at Aalborg University Hospital. The purpose of the project is to ad focus on nutrition to reduce the weight loss induced by chemotherapy. And also minimize the need for tube feeding formula and parenteral nutrition.Our intend is to change the hospitalised child’s perception of food, to generate new knowledge and create the settings for, how the meal that favours the children’s needs and wishes, can be implemented into the paediatrics ward.The project is an interdisciplinary project in co- opera-tion with the paediatric oncology ward, the hospital kitchen and the company Unisans. Both parents and children have been included in the project with interviews regarding wishes and needs concerning the children’s diet. It has been studied, when the children’s nutritional value is most threatened.A new kitchen has been build, where the families can cook and a new food concept has been developed with better content and more exciting food serving.

In addition, a new pamphlet with inspiration has been developed.Food shops where parents and children have been cooking with a sense coach and chefs from Unisans were a part of the project. The “food shop” turned up every 14 days.All of the results have not yet been calculated, but we can conclude that a number of success criteria’s have been fulfilled.Greater fellowship, joy in the eating situation, children who wanted to cook and participate in social gather-ings including food. The children and teenagers have become more outgoing and eat more of the food served. We expect that the project will help improve the children’s psycho-social development.In the future, the experiences from this project can be used when designing new eating environments in paediatric wards.

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O–04

The process of striving for an ordinary, everyday life, in preschool aged children living with cancer, during the first year post diagnos.

Laura Darcy, Paediatric Nurse, PhD student, Maria Björk, Paediatric Nurse. Med Dr., Susanne Knutsson Paediatric Nurse, Med.Dr., & Karin Enskär Paediatric Nurse, Professor of Nursing. Institution of Health Science, University College Borås, Sweden

BackgroundThe majority of children who receive a cancer diagnosis are in the 1-to-6 year age group. Survival rates are high, roughly 75%, but treatment is aggressive and requires long and frequent hospital admissions and causes adverse side effects. Health care focus is shifting from surviving childhood cancer to living with it on a daily basis. The young child’s experiences are crucial to providing evidence based care.

Objectives/AimThe aim of this study was to explore the everyday life of preschool aged children as expressed by the child and their parents during the first year post diagnosis

Methods Interviews were conducted with children and their parents connected to a paediatric oncology unit in Southern Sweden. A qualitative content analysis of interview data from three time points, shortly after diagnosis, six months and one year post diagnosis were made.

ResultsA dramatic change in the young child’s everyday life was described, with experiences of feeling like a stran-ger, under attack and lonely. Experiences over time of gaining control, making a normality of the illness and treatment and feeling lonely were described. This process may be seen as a striving for an everyday life.

ConclusionNurses have a major role to play in the process of striving the child goes through by giving and updating information, making them participary in their care and assuring access to both parents and peers. Addressing these issues and updating them regularly can assist the young child in their transition to living with cancer. Longitudinal studies with young children are vital in capturing their variety of experiences through the cancer trajectory and necessary to ensure quality care.

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O–05

Home care nursing – since 2002 in Helsinki

Eila Huotari. K10 Division of Hematology-Oncology and Stem Cell Transplantation, Helsinki, Finland

K10 Division of Haematology-Oncology and Stem Cell Transplantation includes three workstations: Stem Cell Transplantation Ward, Chemotherapy Ward with Day Hospital and Outpatient Clinic. All these cooperate with our Home Care Unit. The first paediatric cancer unit in Finland was founded in 1982 in Helsinki University Central Hospital.It took 20 years before we were able to begin to man-age some of the nursing activities at the child’s home instead of the hospital. One of our senior nurses started to do home visits: taking blood samples and giving some intravenous medications. Very important group from the beginning were the children in palliative care. Parents who had chosen to take care of their dying child at home needed a lot of support and guidance. We started our Home Care Unit with one nurse who was able to make home visits five days a week; from Monday to Friday. Now we have 1,5 nurses and they

work 7 days a week, however only during the daytime. The aim of our home care nursing is to increase humanity - to the child and the whole family. At home parents often are more open-minded to take guidance and tuition concerning their child’s treatment. Nurse therefore has dedicated time only for the child and the family during the visit without interruptions. We have been trying to develop our home care nursing to respond the family’s needs. One perspective is also the economy: home care is less expensive than hospital care. Our home care nurses consider their work many-sided: they are able to work independently and still be a member of the team. This year we are facing a new exciting challenge: our own small Home Care Unit is planned to unite to the Pediatric Home Care Hospital.

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O–06

Local anesthetic of intramuscular asparaginase

Margareta af Sandeberg. Pediatric Hematology and Oncology, Astrid Lindgrens Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden

BackgroundAsparaginase is an important part in the treatment of acute lymphoblastic leukemia (ALL). In the protocol NOPHO ALL 2000, used between 2002 and 2008, ordinary E.Coli asparaginase was given by the intra-muscular route due to lower frequency of severe allergic reactions than the intra venous. This preparation was hypotonic and painful. As a result of a Danish study from 2005 the routine to inject lidocaine together with asparaginase, was implemented in most of the Nordic countries. In the protocol NOPHO ALL 2008 how-ever, the pegylated form of E coli asparaginase (PEG- asparaginase), dissolved in isotonic sodium chloride was used and the pain due to a hypotonic solution was eliminated. Initially data of PEG-asparaginase activity mixed with lidocaine was missing and the routine with lidocaine was kept at most hospitals although the risk of severe pain had diminished. Lidocaine itself also result in pain when it is injected.

Objectives/AimTo compare children’s/parents’ experiences when intra-muscular PEG asparaginase injection was given with

and without lidocaine and to describe their perceptions of pain and discomfort during the injections.

MethodDuring six month 2012/2013, all children (5-19 years) in a children’s cancer center, with ALL, previously treated with PEG asparaginase with lidocaine and planned for at least two further treatments with PEG asparaginase, was offered to try without lidocaine and subsequently to choose whether the next treatment injection should include lidocaine or not.

Results/ConclusionAll participants (n = 14) chosed to try without lido-caine. Nine reported less discomfort with no lidocaine and three experienced no difference and the majority considered the time factor as most positive. All par-ticipants preferred to continue without the injected lidocaine. Based on the results of this study, lidocaine is no longer injected together with PEG asparaginase at this specific children’s cancer center.

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O–07

Visiting nursing experiences working bedside in the only pediatric oncology ward in Ethiopia

R.N. ped.nurse specialist May Morken, Children’s Department, Outpatient Clinic, Akershus University Hospital, R.N. oncology nurse spacialist and coordinator Hilde Frøland Hauge, Department of Pediatric hematology and Oncology, Children’s Department, Rikshospitalet, University Hospital of Oslo, Norway

Background: Ethiopia is Africa’s second most populous country with 92 million people; the majority live in rural areas. Globally, cancer kills more people than malaria, HIV/AIDS, and TB combined. Governments in low-income countries are scaling up cancer care. In partnership with International Network for Cancer Treatment and Research USA (NGO) since 2011, Tikur Anbessa Hospital in Addis Abeba opened a pediatric oncology department (D7) in April 2013; 27 beds for children up to 12. Currently, 257 children receive treatment, but >3000/year probably have cancer, but are not diagnosed or cannot make it to hospital. The vast majority of families live in extreme poverty and receive free treatment including chemotherapy. Most have had little contact with formal medical care, so many children have advanced disease. Ethiopians speak 90 languages; communication with families can be dif-ficult. Orthodox Christianity is the dominant religion (62%), however, one-third of Ethiopians are Muslim.

Aim:Exploring the value of support, guidance, sharing knowledge and experience with the nurses at D7.

Method:In May 2013, two nurses from Oslo, Norway (both with >30 years experience in pediatric oncology), visited D7 with Julia Challinor from INCTR to explore how and if we could help.

Results/conclusion:The conclusion was that we would return and work bedside for the month of March 2014. Experiences from both our visits will be shared including working in a pediatric oncology unit with frequent shortages of chemotherapy, antibiot-ics, supportive care supplies and equipment. How the nurses’ prioritize their nursing care, including chemotherapy preparation, will be described. Can and should Nordic nurses join forces in supporting colleagues in low-income countries with deficient resources? What are our possibilities based on feedback from the Ethiopian nurses?

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O–08

Study of children’s experiences with venous port access (vap). Need for a nordic study?

Steinunn E. Egeland. Department of Hæmatology and Oncology for children, Department of Peadiatric Medicine, Woman and Children’s Division, Oslo University Hospital, Rikshospitalet, Norway

BackgroundMost children with malignant diseases needcentral venous catheters (CVC´s). There are two different types of CVC´s; Hickman/Broviac (external access) and VAP (internal access)Hickman is visible outside the body, but easy to get access to. Vap is invisible under the skin but has to be punctured with a needle to get access to. We know little about children’s personal experience’s with this procedure. We know, however, that most children fear needles and that some children with cancer find painful procedures as the worst part of their illness.

AimOur aim is to study children’s experiences related to needle access to their VAP. What is the level of anxiety before the port access and pain during the insertion of the needle?

MethodPopulation/inclusion criteria’s:• Children and adolescents (0-18 years) with cancer

or haematological diseases who have had VAP for 3-6 months are included.

• Each child participates only once.• Signed consent

QuestionnaireThe child (if old enough), at least one of the parents and a nurse are asked to fill out a questionnaire before and immediately after the insertion of the needle into VAP. The questionnaire includes 3 different pain score scales validated for children of different ages: FLACC (Face Legs Arms Cry Consolability) for children < 3 years. FPS-R (Faces Pain Scale – Revised) for children > 4-5 years. NRS (Numeric Rating Scales) for children > 8 years.

Results / ConclusionA pilot study of 6 children has been conducted suc-cessfully at Oslo University Hospital.The participants report various levels of anxiety and/or pain and in most cases nurses rate the discomfort higher than children/parents. To gain power, we search for collaborative Nobos/Nopho centres to increase the value of the study.

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O–09

Complications related to gastrostomy in children and adolescents with cancer

Tina Ekängen & Johanna Kjellberg, Pediatric Hematology and Oncology, Astrid Lindgrens Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden

BackgroundChildren and adolescents with cancer are at high risk of suffering from malnutrition, which may affect their tolerance of treatment and even influence the overall survival. At long-term nutrition problems enteral nutri-tion via a gastrostomy is the best choice, even though a gastrostomy causes complications. Fear of gastrostomy complications may be one reason that they are not used to the desired extent in pediatric oncology.

AimThe aim of this study was to identify the presence of gastrostomies and complications related to gastrostomy in children and adolescents with cancer. The study was carried out at the department of pediatric oncology in Stockholm.

MethodMedical records of children and adolescents, 0-20 years, diagnosed with cancer during approximately two and a half year and having a gastrostomy inserted during this period were retrospectively reviewed.

ResultTwenty-two medical records of seven girls and 15 boys were reviewed. Eleven children had their gastrostomy inserted before treatment started and 11 during ongo-ing treatment. Ninety-five percent of the children had gastrostomy-related complications. The most common complications were episodes of granuloma, pain and local infection of the gastrostomy site. The children who received their gastrostomy before treatment started had less major complications than the children who had their gastrostomy inserted during ongoing treatment.

ConclusionChildren and adolescents with cancer who had a gas-trostomy often suffered from complications related to their gastrostomy, however most of the complications were minor. Hopefully this study can support nurses and other caregivers in the nursing care of children with cancer who suffer from malnutrition and those who have a gastrostomy.

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O–10

Kit for symptomatic relief for children in the terminal stage

Marianne Bentsen1 Tone Høivik1, Mikael Donner2, Margrete Einen3,4

1Centre for Pain Management and Palliative Care, Department of Anaesthesia and Surgical Services, Haukeland University Hospital, Bergen, Norway 2The Children’s Clinic, Haukeland University Hospital, Bergen, Norway 3Regional Centre of Excellence for Palliative Care, Western Norway, Haukeland University Hospital, Bergen, Norway 4The Hospital Pharmacy in Bergen, Norway

BackgroundIn the terminal stage unpleasant symptoms such as pain, dyspnea, nausea, respiratory secretion and anxiety / agitation frequently occurs. When children die at home, good pain and symptom management is important to create a safe environment, for both the family and health professionals. Experience with treating children in terminal stage varies. Since 2006, a kit with drugs, equipment for administration and treatment guidelines for adults in the terminal stage has been in use. The experiences are good and a similar kit for children has been asked for.

Materials and methodsA multidisciplinary group consisting of an anesthe-siologist, consultant paediatric oncologist, oncology nurse and hospital pharmacist has adjusted the kit for adult to children. The drugs in the kit and treatment guidelines are updated and adjusted for use in children; the dosing is based on body weight.

The kit contains:1. Instructions for use2. Treatment guidelines 3. A summary of drug details4. Instructions for use of subcutaneous needle

5. Equipment for subcutaneous administration of drugs

6. Guideline and monitoring form for pain man-agement in children

7. Form for evaluating the use and usefulness of the kit

The kit has to be prescribed by a physician, the drugs has to be specified in the prescription. The kit is filled at the local hospital pharmacy. The drugs must be administered by a doctor or nurse.

ConclusionGood pain and symptom relief can be challenging in children in the terminal stage. This kit is hopefully as useful for planned home death in children as the similar kit has been for adults. Treatment guidelines help to give security for the family and for health professionals that rarely treats dying children, and where the drugs chosen and the dosages may be scarcely known. Guidelines and other documents are available in Norwegian from: www.helse-bergen.no/lindrende-behandling

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http://www.helse-bergen.no/lindrendebehandling



P–01 Children and adolescents experience of donating bone marrow / stem cells to surviving siblings

P–02 Establishing common information for adolesents and young adults with cancer and a joint forum for health care personnel

P–03 Improvement project for nutrition support of paediatric hematopoietic stem cell transplant patients

P–04 Oral care and nutrition in children with cancer

P–05 Severe oral mucositis in children diagnosed with cancer in Iceland; prevalence, frequency and risk factors

P–06 Complications of severe oral mucositis in children diagnosed with cancer in Iceland

P–07 Timing the breaking point: a difficult ethical problem in childhood cancer care

P–08 Kit for symptomatic relief for children in the terminal stage

P–09 A Swedish perspective on caring science research in pediatric oncology: a litterateur review

Overview

FREE PAPERS

POSTER PRESENTATIONS

NOPHO / NOBOS


P–01

Children and adolescents experience of donating bone marrow / stem cells to surviving siblings

Carina Rinaldo, Katarina Vallin, Department of Pediatric Oncology and Hematology, Uppsala University Children’s Hospital, Sweden

Background: Family and sibling relationships are affected in both positive and negative ways when a child in the family is afflicted with a severe illness during a long period of time. There are few national studies conducted in Sweden on how siblings who were bone marrow /stem cell donors think and feel about their experience

AimThe aim of this study was to describe children’s and adolescents’ experiences of donating stem cells to a sick sibling in Sweden.

Method: A descriptive interview study with an induc-tive approach was performed using qualitative content analysis. The six participants were of both sexes and between 11-21 years. They were recruited from three different children’s transplant centers, had donated stem cells before the age of 17 and all had surviving siblings. ResultThe theme proud heroes without a choice summarize

the results. The category proud but anxious to be a donor describes a desire and a joy to help, but also concerns how they would endure the procedures and a concern of not being good enough as a donor. They were very anxious for their sick sibling. The category heroes without real choices in need of support highlights the strong family ties make them not having a choice situation for the donation, but a need of support from their environment, healthcare and from receiving information but also all of its weaknesses. Conclusion These donors were happy to contribute to the sibling’s recovery. They were proud and gained a positive view of life from this experience. However the questions remain who will consider the psychological risks of these children and adolescents and if it is right to expose young siblings to this risk.

[email protected] [email protected]

P–02

Establishing common information for adolesents and young adults with cancer and a joint forum for health care personnel

Sunniva Helland1, Hilde Beate Birkeland2, Therese Jørgensen3, Britt Ingunn Wee Sævig4, Rune Hafslund2

1Haukeland Universitety Hospital, Department of Pediatrics, Bergen, Norway 2Department of Oncology and Medical Physics, Bergen, Norway

3Department of Hematology, Bergen, Norway 4The Norwegian Cancer Society, Bergen, Norway

BackgroundAdolescents and young adults face major psychosocial challenges diagnosed with cancer. Early recognition of unmet practical and emotional needs at a critical devel-opmental stage is essential. To facilitate developmentally appropriate and coordinated care, continues support and a good relationship with health care professionals is essential. Moreover, providing necessary information related to the disease and management across different units is fundamental.

Objectives/AimThe main objectives of the project were to 1) develop and evaluate common information leaflet for adoles-cents and young adults with cancer (15-25 years) and 2) to establish a joint forum for health care personnel to facilitate high quality cancer care and successful transfer from pediatric to adult care services.

MethodsNurses from two adult units and from pediatric care were invited to participate in the project. Literature and guidelines were reviewed to identify important information necessary for decisions to be made on the format and content of the leaflet guide. Outcomes to be measured during the evaluation phase were identified. Results /ConclusionFollow-up routines differ between different adult units as well as between the pediatric and adult units. An information leaflet was designed, developed and distributed within the hospital. The leaflet has been revised twice, and efforts to develop individualized care plans are in progress. A formalized forum for further collaboration will be establish to continuously evaluate and promote the outcome of the process. More work is needed to develop additional recommendations to promote successful transition in services.

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NOBOS Poster Presentation NOBOS Poster Presentation





P–03

Improvement project for nutrition support of pae-diatric hematopoietic stem cell transplant patients

Peltola Terttu, authorized nutritionist; Heino Terhi, authorized nutritionist; Bamberg Sirpa, ward manager; Myllymaa Satu, nurse; Leino Jaana, nurse; Arola Mikko, MD; Parto Katriina, MD; Virkki Marjo, project coordinator Paediatric hematology and oncology ward, Tampere University Hospital, Finland

The aim of this improvement project was to develop nutrition support given to malnutrition risk paediatric hematopoietic stem cell transplant (HSCT) patients. Baseline measurements were carried out in spring 2013, literature review included, while in autumn, improve-ment measures, pilot study, final measurements and report were planned and implemented. Surveyed paediatric hematology and oncology ward managers of Finnish University Hospitals saw incoher-ence in both nutrition support and patient brochures.Five patients’ medical records were used to collect information on nutrition status and the implementation of nutrition support during nine 2012 HSCT ward periods. Weight and length were regularly recorded in electronic medical charts, but poorly in electronic growth software. Malnutrition screening was non-existing, and guidelines for nutrition support were only found in the documentation related to small children. All the children received parenteral nutrition two weeks post-transplant, after which they ate mostly favourite foods and snacks, and family foods.Baseline interviews of nurses and doctors indicated varying practices. Use of different growth software

was found confusing. Malnutrition screening was regarded as a workable method, and its more active use recommended. Increase in enteral nutrition was emphasized. The interviewees suggested compiling a patient brochure in line with the Helsinki University Central Hospital (HUCH) guidelines.As a result of the project, malnutrition screening form was updated and converted into electrical format. Documentation praxes were concluded and diet to promote food safety was planned. A HSCT patient nutrition brochure was compiled in co-operation with experts of HUCH. Nutrition counseling given by nutritionist was decided, and a form for monitoring Children’s food intake during enteral or parenteral nutrition developed. Ward’s food service underwent several changes. Due to lack of in-ward HSCT patients during pilot study, the suggested improvements were tested on other paediatric cancer patients. Follow-up will continue till late September 2014.

[email protected]

P–04

Oral care and nutrition in children with cancer

Irina Käyrä and Anna-Maija Mertaniemi. Department of pediatrics University hospital of Oulu, Children’s Hematology and Oncology Ward, Finland

BackgroundOne of the most important issues for the children’s cancer treatment is good nutritional status and oral health.

Objektives/AimThe aim of our study was to evaluate an oral health and nutrition promotion program for children with cancer. The main purpose of our study was to improve children’s oral health and nutrition during cancer treat-ments. By doing this Children’s feel better, children’s treatment can progress as planned and hospitalization can be reduced.

MethodWe started in 2008 systematic co-operation between Children’s hematologic and oncologic ward and Institute of Dentistry. Co-operation occurs so that special child´s dentist visit once a week on the chil-dren’s cancer ward and checks up Children’s health of mouth. If necessary dentist will meet children more. We pay more attention to malnutrition risk. Evaluation form was taken in use at 2013. We pay at least once a week attention to child´s health and nutri-

tional status. In situation of malnutrition, acquiring nutrition balance is primaly recommended by using of gastro-intestional.

Results/ConclusionNow the mucositis treatment is more effective and we have low lever laser in use. Child has better quality of life, because his mouth is painless faster. The child is able to eat and speak. Malnutrition risks early identifying occurs in increased use of Percutaneous Endoscopic Gastrostomy (PEG) since 2008:

2008 12009 02010 22011 32012 12013 5

1/2014 2

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P–05

Severe oral mucositis in children diagnosed with cancer in Iceland; prevalence, frequency and risk factors

Oddný Kristinsdóttir, Barnaspítali Hringsins, Reykjavík, Iceland

BackgroundSevere oral mucositis (3°-4°) is a frequent and severe complication of chemotherapy in children undergo-ing chemotherapy. Limited data is available on the prevalence and how to assess the extent of severe oral mucositis.

AimTo estimate the prevalence of severe oral mucositis in children treated with chemotherapy in Iceland. Also to examine the frequency and risk factors of severe oral mucositis.

MethodA retrospective population-based study was performed. A data recording form was designed to gather informa-tion from patients´ medical records on complications, risk factors, assessment and interventions of severe oral mucositis. The study sample was children from 1 to 18 years of age who received chemotherapy in Iceland from 2002 to 2011. According to the Icelandic Cancer Registry, 120 children were diagnosed with cancer during this period, of which 64 were included in the current study. Oral mucosal assessment scale WHO and NIC were used to identify children with severe oral mucositis.

ResultsTwenty five (39%) children developed severe oral mucositis, each up to 6 times (a total of 60 episodes). Nine children (36%) had severe oral mucositis once, but one six times. Children with severe oral mucositis were significantly older (p = 0.008) than those with mild or no oral mucositis. Sixty percent of those developing severe oral mucositis were boys. The highest frequency of severe oral mucositis was among patients with acute leukemia, malignant bone tumors and lymphoma. A significant correlation was found between the number of days with neutropenia and the number of days with symptoms of severe oral mucositis (r = 0.736, p <0.0001).A large proportion of children who are treated with chemotherapy in Iceland develop severe oral mucositis. This is in agreement with studies from other countries. Incidence figures are inconsistent, most likely due to different measuring methods.

KeywordSevere oral mucositis, chemotherapy, prevalence, risk factors, children.

[email protected]

P–06

Complications of severe oral mucositis in children diagnosed with cancer in Iceland

Oddný Kristinsdóttir, Barnaspítali Hringsins, Reykjavík, Iceland

BackgroundSevere oral mucositis (3°-4°) is a frequent and severe complication of chemotherapy in children undergoing chemotherapy. Limited data is available on the com-plications and consequences of severe oral mucositis on children.

Aim To examine the symptoms and complications of severe oral mucositis in children treated with chemotherapy in Iceland.

MethodA retrospective population-based study was performed. A data recording form was designed to gather informa-tion from patients´ medical records on complications, risk factors, assessment and interventions of severe oral mucositis. The study sample was children from 1 to 18 years of age who received chemotherapy in Iceland from 2002 to 2011. According to the Icelandic Cancer Registry, 120 children were diagnosed with cancer during this period, of which 64 were included in the current study. Oral mucosal assessment scale WHO and NIC were used to identify children with severe oral mucositis.

Results

Twenty five (39%) children developed severe oral mucositis (a total of 60 episodes). In all episodes the children had pain in the mouth and in 60% of the episodes in the throat. In 95% of the episodes the children could not eat solid food. The mean number of symptoms was 3.5. Most children (76%) received parenteral nutrition or enteral (NG-tube) nutrition because of pain in the mouth or throat. Blood cultures were drawn in 80% of the episodes and antibiotics administered intravenously in 77%. Bacteria were cultured in 21%, of which 50% were considered contamination. The peak CRP value and peak temperature were significantly higher for severe oral mucositis compared to milder cases.Children with severe oral mucositis are severely affected. Pain is common and serious, impaired nutritional intake is common, and the majority of children are nourished intravenously or via NG-tube. Children are at a increased risk of infections and a majority of cases requires antibiotics intravenously.

KeywordSevere oral mucositis, chemotherapy, complications, symptoms, children.

[email protected]



P–07

Timing the breaking point: a difficult ethical problem in childhood cancer care

Bartholdson, C., Lützén, K., Blomgren, K., Pergert, P. Women and Children’s Health, Karolinska Institutet, Children’s Cancer Research Unit, Astrid Lindgren’s Hospital, Stockholm, Sweden

Background The treatment for paediatric cancer is physically, socially and psychologically demanding, and often gives rise to ethical problems about treatment and care.

ObjectiveThe purpose of this presentation is to describe a difficult ethical problem frequently experienced in childhood cancer care.

MethodHealth care professionals from three paediatric units, which all treat children with cancer, at a major hospital in Sweden answered a study-specific questionnaire. Qualitative content analysis was used to analyse answers to open-ended questions.

Results / ConclusionDifferent perspectives affected which treatment was considered to be ethically right, especially when the treatment was of uncertain benefit for the patient. Writing about the breaking point, they described an invisible point in time when the transition from cura-tive to palliative treatment occurred. They expressed that opinions diverged between physicians, nurses

and parents about when the breaking point occurred and the breaking point was a major concern for all professional groups and often led to conflicts in the team. Physicians had to make the decisions regard-ing limitations of life-sustaining treatment and the changed aim of the treatment. Uncertainty aroused about when to make this decision to achieve the best possible care for the patient. Nurses wished for the breaking point to appear earlier in the care process in relation to the perceived suffering of the children. Parents were sometimes perceived to be blinded by the fear of losing their child and by grief, resulting in them wanting to continue with life-sustaining treatment as long as possible. Even though all health care professionals were focus-ing on what they thought was the best for the child, they ended up having different perspectives of when the breaking point occurred. There could be various reasons for the differences including professional and cultural as well as personal values or preferences.

[email protected]

P–08

Kit for symptomatic relief for children in the terminal stage

Marianne Bentsen1Tone Høivik1, Mikael Donner2, Margrete Einen3,4

1Centre for Pain Management and Palliative Care, Department of Anaesthesia and Surgical Services, Haukeland University Hospital, Bergen, Norway 2The Children’s Clinic, Haukeland University Hospital, Bergen, Norway 3Regional Centre of Excellence for Palliative Care, Western Norway, Haukeland University Hospital, Bergen, Norway 4The Hospital Pharmacy in Bergen, Norway

BackgroundIn the terminal stage unpleasant symptoms such as pain, dyspnea, nausea, respiratory secretion and anxiety / agitation frequently occurs. When children die at home, good pain and symptom management is important to create a safe environment, for both the family and health professionals. Experience with treating children in terminal stage varies. Since 2006, a kit with drugs, equipment for administration and treatment guidelines for adults in the terminal stage has been in use. The experiences are good and a similar kit for children has been asked for.

Materials and methods A multidisciplinary group consisting of an anesthe-siologist, consultant paediatric oncologist, oncology nurse and hospital pharmacist has adjusted the kit for adult to children. The drugs in the kit and treatment guidelines are updated and adjusted for use in children; the dosing is based on body weight.

The kit contains:1. Instructions for use2. Treatment guidelines 3. A summary of drug details4. Instructions for use of subcutaneous needle

5. Equipment for subcutaneous administration of drugs

6. Guideline and monitoring form for pain man-agement in children

7. Form for evaluating the use and usefulness of the kit

The kit has to be prescribed by a physician, the drugs has to be specified in the prescription. The kit is filled at the local hospital pharmacy. The drugs must be administered by a doctor or nurse.

ConclusionGood pain and symptom relief can be challenging in children in the terminal stage. This kit is hopefully as useful for planned home death in children as the similar kit has been for adults. Treatment guidelines help to give security for the family and for health professionals that rarely treats dying children, and where the drugs chosen and the dosages may be scarcely known. Guidelines and other documents are available in Norwegian from: www.helse-bergen.no/lindrendebehandling

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P–09

A Swedish perspective on caring science research in pediatric oncology: a litterateur review

Karin Enskär, RN, PhD, Professor of Nursing, Maria Bjork, RN, PhD, Laura Darcy, RN, MPH, School of Health Sciences, Jonkoping University Sweden and CHILD research Group, Jonkoping University, Sweden

BackgroundThe body of research-based knowledge in pediatric caring sciences has been increasing thanks to a dra-matic improvement in outcomes related to research and advances in treatment.

Objectives/AimThe aim of this review was investigate the content of published studies in pediatric oncology related to caring sciences.

MethodA systematic litterateur review of 137 published arti-cles on pediatric oncology related to caring science in Sweden was performed.

Results / ConclusionThe result shows that most of the studies were descrip-tive or comparative studies with a quantitative design. Most of them had parents in focus, and only 22% had focus on the child. Most of the studies investigated well-being, using questionnaires or interviews. The result, as stated in the articles, demonstrated that the child´s disease has affected the wellbeing of all people coming

in contact with the child, in both positives and negative ways. Also the child´s disease causes distress related to physical, psychological, existential and social aspects. Several mediating factors for the experience of distress and wellbeing were found, as; disease and treatment severity, gender, time since diagnose, and the use of internal and external support. Frequent reported health promoting aspects were: family togetherness, coping strategies and engaging in activities and normal life, as well as quality of care; as emotional support, informa-tion and family participation in care. Suggestions for clinical implications, stated in the articles, were often described in a diffuse manner making translation into clinical practice difficult. However, some areas of clinical implications could be identified and described. To reflect the child’s perspective in pediatric oncology requires that future researchers take on the challenge of including children. The biggest challenge for the future would be to make a shift from explorative stud-ies to intervention studies. There is an urgent need to transform research results into clinical practice.

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Velkommen til maleriutstilling i Kreftforeningens lokaler i forbindelse med NOBOS og NOPHO´s nordiske konferanse i Bergen i mai 2014.

NOPHO/NOBOS 2014 Bergen9th - 13th May

Åpning: fredag 9. mai kl. 1800

Møt kunstnerne til samtale og visning: lørdag 10. mai kl. 1400søndag 11. mai kl 1800

Kreftforeningens lokaler Strandgaten 62 i Bergen HELGjennom maleriene søker duoen å inspirere og motivere betrakteren gjennom visuelle fortellinger. Som for eksempel om øyeblikkene der et med-menneske eller en hendelse gir livet ny retning, der gleden ved å virke, det å bety noe for noen eller noe kjennes altomfattende. Ofte formidles det glade, energiske og humoristiske, av og til det såre, sorgfulle og vanskelige.

Bringager & Malmstrøm Malerduoen

Eva Malmstrøm [email protected]

tlf: 932 51 572Hanne Bringager

[email protected] tlf: 930 95 922

NOBOS Poster Presentation

124 N O P H O / N O B O S A N N U A L M E E T I N G – B E R G E N 2 0 1 4


- å bedre barnas helhetlige behandlings- og

rehabiliteringstilbud

- å støtte og tilrettelegge forholdene for familiene

- å samarbeide med leger, pleiepersonell og andre

som har omsorg for barna

- å drive informasjonsvirksomhet omkring

sykdommen og Barnekreftforeningen

- å søke positivt samarbeid med andre foreninger

der dette er naturlig

TELEFON: [email protected]

BESØKSADRESSE: Øvre Vollgate 11, 0158 OsloPOSTADRESSE: Postboks 4 Sentrum, 0101 OsloORG. NUMMER: 985 550 999www.barnekreftforeningen.no

Formål


Meeting venueRadisson Blu Royal Hotel, BergenBryggen 5, 5003 Bergen | radissonblu.com/royalhotel-bergen

Photos: Radisson Blu Royal Hotel, Bergen


http://www.radissonblu.com/royalhotel-bergen

NOPHOAnnual Meeting

Nordic Society of Paediatric Haematology and Oncology

2015

May 22nd - May 26th Oulu, Finland

WELCOME

Main topics

• NHL: genetics, allotransplant for ALCL, new drugs in NHL

• Immunodeficiencies: diagnostic challenges, SCT and viral infections after SCT

• Fertility and pregnancy after childhood cancer

• Educational session: Genetics of MDS, Immunodeficiencies, treatment of osteosarcoma

Please see more info http://www.nopho.org/

Organizing committee:Merja Möttönen Satu Lehtinen Hanna Juntti

Riitta Niinimäki Anne HekkalaMinna Honkila

Conference secretariat Aira Raudasoja (Ms)

Congress Manager, CongCreator CC [email protected]

tel +358 (0)500 604 686

VenueRadisson Blu Hotel

Hallituskatu 1, 90100 Oulu, Finland


Thank you

for attending!

NOPHO / NOBOSnopho.org/.../NOPHO-NOBOS-Programbok-web.pdf · 2 NOPHO / NOBOS MEETING AND CONGRESS...

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Transcript of NOPHO / NOBOSnopho.org/.../NOPHO-NOBOS-Programbok-web.pdf · 2 NOPHO / NOBOS MEETING AND CONGRESS...